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Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type
Guía para el tratamiento preventivo del ictus isquémico y AIT (II). Recomendaciones según subtipo etiológico
B. Fuentes
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hplapazneuro@meditex.es

Corresponding author.
, J. Gállego, A. Gil-Nuñez, A. Morales, F. Purroy, J. Roquer, T. Segura, J. Tejada, A. Lago, E. Díez-Tejedor, representing the ad hoc committee of the SEN Study Group for Cerevrovascular Diseases ◊, M. Alonso de Leci¿nana, J. Álvarez-Sabin, J. Arenillas, S. Calleja, I. Casado, M. Castellanos, J. Castillo, A. Dávalos, F. Díaz-Otero..., J.A. Egido, J.C. López-Fernández, M. Freijo, A. García Pastor, F. Gilo, P. Irimia, J. Maestre, J. Masjuan, J. Martí-Fábregas, P. Martínez-Sánchez, E. Martínez-Vila, C. Molina, F. Nombela, M. Ribó, M. Rodríguez-Yañez, F. Rubio, J. Serena, P. Simal, J. VivancosVer más
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            "apellidos" => "Egido"
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            "apellidos" => "L&#243;pez-Fern&#225;ndez"
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            "apellidos" => "Freijo"
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            "apellidos" => "Maestre"
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            "apellidos" => "Mart&#237;nez-S&#225;nchez"
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            "apellidos" => "Rib&#243;"
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    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Gu&#237;a para el tratamiento preventivo del ictus isqu&#233;mico y AIT &#40;II&#41;&#46; Recomendaciones seg&#250;n subtipo etiol&#243;gico"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In Spain&#44; cerebrovascular diseases &#40;CVD&#41; are the leading cause of death in women&#44; the third most frequent in men&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and the most common cause of disability&#46; The measures we describe here are designed to prevent both first-ever ischaemic strokes &#40;IS&#41; and future episodes in patients who have already suffered a stroke&#46; We will also consider measures aimed at reducing overall vascular risk in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Due to the length of this article&#44; we decided to publish it in 2 parts&#46; The first part presented a review of the risk factors for ischaemic stroke<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and any modifications that would need to be made to prevent IS&#46; In this second part&#44; we will specify different preventive treatments according to the stroke subtype&#46; Recommendations for each section are shown in tables for better readability&#46; Levels of evidence and recommendation grades are based on the classification proposed by the Centre for Evidence Based Medicine at the University of Oxford<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; To facilitate reading&#44; we have included transient ischaemic attack &#40;TIA&#41; in our definition of ischaemic stroke&#46; This practice coincides with current criteria&#46; Therefore&#44; all recommendations included in these clinical practice guidelines are directed at preventing focal cerebral ischaemia in general&#44; without distinguishing between cerebral infarct and TIA&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ischaemic stroke associated with large-vessel arteriosclerosis and small-vessel disease &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;</span><p id="par0010" class="elsevierStylePara elsevierViewall">Risk factors &#40;RF&#41; should be modified&#46; In addition&#44; antiplatelet drugs are recommended along with carotid endarterectomy or percutaneous transluminal angioplasty in selected patients&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Antiplatelet drugs</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Acetylsalicylic acid &#40;ASA&#41;</span><p id="par0015" class="elsevierStylePara elsevierViewall">ASA reduces the absolute risk of stroke&#44; acute myocardial infarction &#40;AMI&#41;&#44; or vascular death by 13&#37; to 25&#37; compared to placebo&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a> This is a first-choice antiplatelet drug and the recommended dose is 100 to 300<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clopidogrel</span><p id="par0020" class="elsevierStylePara elsevierViewall">In patients with atherosclerotic disease &#40;AMI&#44; stroke&#44; or peripheral artery disease&#41;&#44; ASA is slightly more effective for reducing the risk of stroke&#44; AMI&#44; and vascular death &#40;decrease in relative risk of 8&#46;7&#37;&#41; with fewer digestive tract haemorrhages and the same risk of neutropenia&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> A sub-analysis in the CAPRIE study found that clopidogrel was no more effective than ASA in patients with a prior stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However&#44; clopidogrel was more effective in the subgroup of patients with a history of symptomatic atherosclerosis &#40;prior IS or AMI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> These observations should be considered with care&#44; given that the CAPRIE study was not designed for subgroup analysis&#46; Clopidogrel dosed at 75<span class="elsevierStyleHsp" style=""></span>mg&#47;day is considered a first-choice treatment&#44; especially in patients with ASA intolerance&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Triflusal</span><p id="par0025" class="elsevierStylePara elsevierViewall">In doses of 600<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; triflusal has a similar efficacy to that of ASA with fewer haemorrhagic complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;14</span></a> It is also considered a first-choice treatment&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Dipyridamole</span><p id="par0030" class="elsevierStylePara elsevierViewall">Although dipyridamole reduces stroke recurrence by 18&#37; compared to placebo&#44; it is not used in monotherapy because it has no effect on vascular death&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Cilostazol</span><p id="par0035" class="elsevierStylePara elsevierViewall">The Second Cilostazol Stroke Prevention Study &#40;CSPS2&#41;&#44; conducted in Asian patients with IS&#44; showed that cilostazol &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41; was noninferior and could even be superior to ASA &#40;81<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41; for preventing stroke recurrences due to being associated with a lower frequency of haemorrhagic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> A recent Cochrane meta-analysis confirms that cilostazol was superior to ASA for preventing stroke recurrence in patients with IS&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Other antiplatelet drugs under study</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Sarpogrelate</span><p id="par0040" class="elsevierStylePara elsevierViewall">Sarpogrelate&#39;s efficacy for secondary stroke prevention resembles that of ASA&#44; and its haemorrhagic complication rate is lower&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">SCH 530348</span><p id="par0045" class="elsevierStylePara elsevierViewall">Follow-up on stroke patients was interrupted prematurely in the TRA-TIMI50 study as there was an increased risk of haemorrhage&#46; The drug is still being investigated for patients with ischaemic heart disease or peripheral artery disease&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Prasugrel</span><p id="par0050" class="elsevierStylePara elsevierViewall">Compared to clopidogrel&#44; prasugrel significantly reduced cardiovascular episodes in patients at moderate to high risk for acute coronary syndrome and treated with percutaneous coronary angioplasty&#46; It is associated with a higher number of haemorrhagic complications&#59; mortality was similar in both groups&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> This drug is not recommended in patients in early phases after stroke or TIA&#44; and there have been no trials investigating its potential for secondary stroke prevention&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ticagrelor</span><p id="par0055" class="elsevierStylePara elsevierViewall">Compared to clopidogrel&#44; ticagrelor reduced the number of AMI and vascular deaths or deaths due to other causes among patients with acute coronary syndrome&#46; While there were no differences in the overall number of major haemorrhagic complications&#44; the percentage of fatal cerebral haemorrhages was lower&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> No studies have been conducted to specifically examine secondary stroke prevention with ticagrelor&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Associations of antiplatelet drugs</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">ASA and dipyridamole</span><p id="par0060" class="elsevierStylePara elsevierViewall">The ESPS2 and ESPRIT studies were the first to identify the combination of ASA and dipyridamole &#40;ASA&#47;DPR&#41; as being superior to ASA for preventing vascular episodes&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a> However&#44; the validity of these results has been called into question due to methodology problems&#46; A systematic review showed that the ASA&#47;DPR combination&#44; compared to ASA alone&#44; decreased the risk of a new&#44; non-fatal stroke by 23&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The PRoFESS study compared clopidogrel 75<span class="elsevierStyleHsp" style=""></span>mg&#47;d to ASA 25<span class="elsevierStyleHsp" style=""></span>mg&#47;DPR 200<span class="elsevierStyleHsp" style=""></span>mg &#40;extended release&#44; administered twice daily&#41;&#46; That study found that ASA&#47;DPR was not superior to clopidogrel in the areas of secondary stroke prevention&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> functional recovery&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> or the potential development of cognitive impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">ASA and clopidogrel</span><p id="par0065" class="elsevierStylePara elsevierViewall">The MATCH study examined the efficacy of the combination of ASA 75<span class="elsevierStyleHsp" style=""></span>mg&#47;d and clopidogrel 75<span class="elsevierStyleHsp" style=""></span>mg&#47;d &#40;ASA&#47;CLP&#41;&#44; compared to clopidogrel alone&#44; in patients with a history of stroke or TIA&#46; The combination was not superior to clopidogrel and it was associated with a significantly higher risk of haemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Additionally&#44; the CHARISMA<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> study in patients with clinically evident vascular disease or multiple RFs did not show ASA&#47;CLP to have greater efficacy for stroke recurrence reduction than ASA monotherapy&#46; One of the objectives of the study Secondary Prevention of Small Subcortical Strokes &#40;SPS3&#41;&#44; currently underway&#44; is to evaluate the efficacy of ASA&#47;CLP in reducing stroke recurrence in patients with small vessel disease&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Other combinations</span><p id="par0070" class="elsevierStylePara elsevierViewall">Additional combinations of anti-platelet drugs have also been tested&#44; including ASA&#47;DPR&#47;CLP and ASA&#47;CLP with glycoprotein IIb&#47;IIIa inhibitors&#46; Data were insufficient in both cases to yield recommendations for stroke prevention&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Oral anticoagulant agents</span><p id="par0075" class="elsevierStylePara elsevierViewall">The SPIRIT study<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> compared high-intensity oral anticoagulants &#40;3&#46;0-4&#46;5 INR&#41; to ASA &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#46; It was terminated prematurely due to a high volume of haemorrhagic complications in the anticoagulant group&#46; The WARSS<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> study compared 325<span class="elsevierStyleHsp" style=""></span>mg&#47;d ASA to warfarin adjusted for an INR target of 1&#46;4 to 2&#46;8 and had identified no differences at the 2-year point&#46; The ESPRIT study concluded that medium-intensity oral anticoagulants &#40;2-3 INR&#41; were no more effective than ASA for secondary prevention of IS&#44; and that any possible protective effect was cancelled out by the number of haemorrhagic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> One systematic review showed that anticoagulants &#40;INR of up to 2&#46;6&#41; displayed no advantages compared to antiplatelet treatment with regard to either risk of death by vascular causes or overall mortality&#46; Furthermore&#44; intensive anticoagulant treatment &#40;3-4&#46;5 INR&#41; is associated with a significant increase in total mortality and severe haemorrhagic episodes&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Data from studies or specific cases of non-cardioembolic stroke appear below&#46;</p><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Stenosis of the intracranial arteries</span><p id="par0085" class="elsevierStylePara elsevierViewall">The WASID study for symptomatic intracranial stenosis was interrupted prematurely since warfarin showed higher rates of haemorrhagic complications and no benefits compared to ASA dosed at 1300<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Basilar artery stenosis</span><p id="par0090" class="elsevierStylePara elsevierViewall">An analysis of the WASID study suggested that these patients might benefit from anticoagulant treatment even though differences were not significant&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Stroke recurrence despite antiplatelet treatment</span><p id="par0095" class="elsevierStylePara elsevierViewall">Oral anticoagulants have not shown any benefits in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></span></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Vascular interventional procedures</span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Extracranial carotid artery stenosis</span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Carotid endarterectomy</span><p id="par0100" class="elsevierStylePara elsevierViewall">Endarterectomy offers more advantages than medical treatment in cases of symptomatic carotid stenosis &#62;<span class="elsevierStyleHsp" style=""></span>70&#37;&#46; The NASCET study shows an improvement of 17&#37; at the 2-year mark<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> and ECST shows 14&#37; improvement at the 3-year mark&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> For moderate cases of stenosis &#40;50-69&#37;&#41;&#44; the benefit of carotid endarterectomy is less pronounced &#40;4&#46;5&#37; reduction in absolute risk at 5 years&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a>&#59; there is no significant benefit for stenosis &#60;<span class="elsevierStyleHsp" style=""></span>50&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;39</span></a> In contrast&#44; a meta-analysis that includes the ECST and NASCET studies points to higher benefits from endarterectomy in men&#44; patients older than 75 years&#44; and patients undergoing the procedure within 2 weeks of the stroke or TIA&#59; it is less effective at later dates&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> It is currently indicated in patients with symptomatic carotid stenosis of 70&#37; to 99&#37; and an additional life expectancy of more than 5 years&#44; provided that the hospital in question has a surgical morbidity and mortality rate of less than 6&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#8211;43</span></a> Endarterectomy may be considered in patients with symptomatic carotid stenosis of 50&#37; to 69&#37;&#44; but certain variables may affect the risk-benefit balance&#58; female sex &#40;no clear benefit in clinical trials&#41;&#59; initial manifestation as hemispheric IS &#40;better results than in retinal ischaemia&#41;&#59; or presence of a contralateral carotid occlusion&#44; which is associated with a greater preoperative risk although benefits remain&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a> Medical treatment without endarterectomy is indicted in patients with carotid stenosis &#60;<span class="elsevierStyleHsp" style=""></span>50&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#8211;43</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Percutaneous transluminal angioplasty</span><p id="par0105" class="elsevierStylePara elsevierViewall">This technique has shown good results in patients with fibromuscular dysplasia&#44; lesions due to radiotherapy&#44; or restenosis following endarterectomy&#46; It has been suggested as a treatment alternative for stenosing atherosclerosis&#46; The CAVATAS study showed similar efficacy and safety results for percutaneous transluminal angioplasty and endarterectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Technical advances include specific angioplasty balloons&#44; stents&#44; and most recently&#44; distal protection devices&#46; The SAPPHIRE study of carotid angioplasty and stenting showed that the technique was superior to endarterectomy in patients with a high level of surgical risk and symptomatic or asymptomatic carotid stenosis&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> However&#44; early interruption of the EVA-3S study due to high rates of 30-day mortality or stroke in the carotid angioplasty group&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> and the SPACE study&#39;s failure to demonstrate that the technique was noninferior to carotid endarterectomy may constitute reasons to question carotid angioplasty as a safe alternative&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> However&#44; long-term follow-up &#40;2&#8211;4 years&#41; has shown similar levels of reduction of ipsilateral IS for both techniques&#44; although researchers stress the need to improve short-term safety results of carotid angioplasty and stenting&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">48&#44;49</span></a> A meta-analysis indicates that endovascular treatment is associated with a modest increase in stroke and death rates 30 days after the procedure&#44; with no significant intergroup differences in rates of incapacitating stroke or death at 30 days&#46; On the other hand&#44; surgical treatment is associated with a significant increase in cranial nerve palsy and AMI&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> The ICSS study<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> found a 3&#46;3&#37; difference in absolute risk of stroke&#44; death&#44; or AMI at 120 days that pointed to endarterectomy as the superior technique&#46; The CAVATAS study<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> identified a higher incidence of non-perioperative stroke in patients with endovascular treatment &#40;21&#46;1&#37;&#41; than in those treated with endarterectomy &#40;15&#46;4&#37;&#41;&#46; This difference was observed even after the 2-year randomisation process&#44; and it may be explained by the higher incidence of restenosis following angioplasty&#46; Only a small group of patients in the CAVATAS study underwent stenting &#40;22&#37;&#41;&#46; The true long-term incidence rate for post-stent restenosis is unknown&#46; The CREST study&#44; conducted in patients with high-grade stenosis&#44; whether symptomatic &#40;53&#37;&#41; or asymptomatic &#40;47&#37;&#41;&#44; observed no significant differences regarding the study&#39;s main objective&#46; During the periprocedural period&#44; however&#44; there was a greater risk of non-disabling stroke with stenting&#44; and a greater risk of AMI with endarterectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> One important consideration is that over time &#40;4 years&#41;&#44; the rates of stroke recurrence were very low with both treatment options&#46; This may be partially explained by the high percentage of asymptomatic patients in this group&#46; Factors associated with a higher risk of periprocedural stroke or death with carotid angioplasty include male sex&#44; age &#62;<span class="elsevierStyleHsp" style=""></span>70 years&#44; prior stroke&#44; and having experienced a stroke rather than a TIA&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">48&#44;54</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In cases of symptomatic stenosis of the common carotid artery&#44; the reasonable options are revascularisation by carotid angioplasty&#44; direct arterial reconstruction&#44; or extra-anatomic bypass grafting&#46; However&#44; available evidence is insufficient to make recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Extracranial vertebral artery stenosis&#59; subclavian artery stenosis</span><p id="par0115" class="elsevierStylePara elsevierViewall">Indications for revascularisation in cases of proximal vertebral artery stenosis are infrequent&#59; generally speaking&#44; the contralateral artery will supply the basilar artery sufficiently&#46; In cases of stroke recurrence despite appropriate medical treatment&#44; surgical or endovascular treatment may be considered&#46; Evidence is insufficient to recommend one procedure over another&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;55</span></a> Surgical options include trans-subclavian vertebral endarterectomy&#44; transposition of the vertebral artery to the ipsilateral common carotid artery&#44; and reimplantation of the vertebral artery using a venous graft extension to the subclavian artery&#46; The only randomised study on endovascular treatment in patients with vertebral artery stenosis was CAVATAS&#44; which randomised 16 patients to receive either endovascular treatment and medical treatment&#44; or medical treatment alone&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> In cases of cerebral ischaemia in the posterior cerebral territory due to subclavian artery stenosis&#44; doctors may consider the possibility of a carotid-subclavian extra-anatomic bypass for cases with low surgical risk&#46; Percutaneous angioplasty and stenting should be considered in cases with an elevated risk of surgical complications&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Intracranial arterial stenosis</span><p id="par0120" class="elsevierStylePara elsevierViewall">The WASID trial found a yearly risk of stroke of 11&#37; despite the best medical treatment&#59; this figure was 19&#37; in the subgroup with stenosis &#8805;<span class="elsevierStyleHsp" style=""></span>70&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> These patients present a high risk of recurrent ischaemia in the territory of the stenosed artery&#46; This is also seen in the vertebrobasilar territory &#40;12&#37; at 1 year and 15&#37; at 2 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> In 2005&#44; the FDA approved the use of the Wingspan stent system&#44; which is effective in 96&#46;7 to 98&#46;8&#37; of all cases and has a 30-day complication rate of 6&#46;1 to 9&#46;6&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> In one European registry&#44; 25 to 30&#37; of patients experienced restenosis &#40;mostly asymptomatic&#41;&#44; while 4&#46;8&#37; experienced an incapacitating stroke&#46; The mortality rate was 2&#46;2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> Researchers recently halted the SAMMPRIS study &#40;Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis&#41;&#46; The study compared angioplasty and the Wingspan stent system associated with medical treatment &#40;modification of risk factors and ASA&#47;CLP combination treatment&#41; to medical treatment alone in patients with symptomatic intracranial stenosis &#62;<span class="elsevierStyleHsp" style=""></span>70&#37; and IS in the first 30 days&#46; Recruitment was stopped after 451 patients&#44; rather than the anticipated 764 since significant benefits were found for the medical treatment group&#44; which yielded lower rates of stroke or death at 30 days &#40;5&#46;8&#37; in the medical treatment group vs 14&#37; in the Wingspan group&#41;&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Extra-intracranial arterial anastomosis</span><p id="par0125" class="elsevierStylePara elsevierViewall">Approximately 10&#37; of patients with non-disabling stroke present occlusion or stenosis of the internal carotid artery or middle cerebral artery&#46; Effects of this condition might be reduced by anastomosing the superficial temporal branch of the external carotid artery to an extra-intracranial bypass&#44; although the only completed clinical trial yielded negative results&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> Regardless of the effectiveness this technique has displayed in selected patients with giant aneurysm of the internal carotid artery&#44; or moyamoya disease in young patients&#44; there are currently no indications for extra-intracranial anastomosis as a means of preventing stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> Results from the clinical trial Carotid Occlusion Surgery Study&#44; presented at ISC 2011&#44; did not show surgery to be an effective means of preventing stroke recurrence at 2 years because of the low recurrence rate in the non-surgical group&#46;</p></span></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Ischaemic stroke of cardioembolic origin &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;</span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Nonvalvular atrial fibrillation</span><p id="par0130" class="elsevierStylePara elsevierViewall">Current treatment follows 2 strategies&#58; prevention of thromboembolism using antithrombotic agents&#44; and treatment of the FA itself&#44; including stabilising both heart rate and rhythm&#46; Furthermore&#44; new non-pharmacological treatments are being developed to decrease risk of stroke in patients with non-valvular AF&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">62&#8211;64</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Oral anticoagulant agents</span><p id="par0135" class="elsevierStylePara elsevierViewall">The European Atrial Fibrillation Trial &#40;EAFT&#41; in stroke patients with non-valvular AF showed a 66&#37; decrease in the IS recurrence rate in the warfarin group&#44; vs a 15&#37; decrease in the ASA group &#40;300<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a> The number needed to treat &#40;NNT&#41; to avoid one stroke per year is 14 for warfarin and 50 for ASA&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a> While vitamin K antagonists &#40;VKA&#41; are effective&#44; they pose significant problems in clinical practice and are consequentially often underused&#46; Vitamin K antagonists may also be dosed incorrectly due to their delayed action and metabolism&#44; narrow therapeutic range&#44; the considerable variation in their metabolism process and numerous interactions with foods and other drugs&#44; the presence of genetic polymorphisms that affect the dosing requirements&#44; and the need for regular coagulation monitoring and frequent dose adjustments&#44; which generates additional costs&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> As a result&#44; only 10&#37; to 18&#37; of these patients have an appropriate INR&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67&#44;68</span></a> Risk of haemorrhage is another severe problem with VKA treatment&#46; This risk can be reduced by treating AHT and monitoring INR&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> If the range is appropriate &#40;2-3 INR&#41;&#44; the risk of cerebral haemorrhage is 0&#46;5&#37; per year with a NNT of 200&#59; this is acceptable when compared to the NNT of 14 for avoiding a stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a> We recommend using the HAS-BLED scale of risk of severe haemorrhage to assess the risk-benefit balance of oral anticoagulants&#46; Patients with scores &#8805;<span class="elsevierStyleHsp" style=""></span>3 are considered to be at high risk&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">69</span></a> On the other hand&#44; despite risk of haemorrhage&#44; oral anticoagulants show clear benefits in patients over 85 and with AF&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">New anticoagulants are currently available &#40;thrombin and factor X inhibitors&#41; that provide the added advantage of not requiring INR level monitoring&#46; Dabigatran dosed at 100<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h has shown similar efficacy to warfarin treatment for stroke reduction&#46; It is associated with a lower frequency of major haemorrhages&#59; at doses of 150<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; it is more effective than warfarin for stroke reduction with similar haemorrhage rates&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> Dabigatran is easy to administer&#44; as it has set doses and does not require monitoring&#46; Analysis of the subgroup with IS showed efficacy results for dabigatran that were similar to those for the total group&#44; but tending towards superiority over warfarin&#46; Both dabigatran dosages also showed a significantly lower risk of intracranial haemorrhage and haemorrhagic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a> In a cost-effectiveness study in patients older than 65 years with a CHADS2 score &#8805;<span class="elsevierStyleHsp" style=""></span>2&#44; dabigatran proved itself to be an alternative to warfarin based on prices in the USA&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> Dabigatran has been approved by the FDA and by Health Canada&#44; and it is pending approval in Europe&#46; European and AHA guidelines<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">63&#44;74</span></a> place dabigatran on par with VKAs for stroke prevention in patients with AF&#46; Doses of 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h are indicated in patients with a lower risk of cardioembolism or a higher risk of haemorrhage &#40;very advanced age&#44; poorly managed AHT&#44; prior cerebral haemorrhage&#44; neuroimaging evidence of leukoaraiosis or cerebral microhaemorrhage&#44; or HAS-BLED score &#8805;<span class="elsevierStyleHsp" style=""></span>3&#41;&#46; Doses of 150<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h are indicated for patients with a higher risk of cardioembolism or INR below the therapeutic range despite VKA treatment&#44; or where there are other VKA-related problems&#46; For secondary prevention of cardioembolic stroke&#44; 150<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h is an appropriate dose in patients with a HAS-BLED score &#60; 3 or stroke recurrence despite correct treatment with VKAs&#46; The dose of 110<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h is recommended for HAS-BLED scores &#8805;<span class="elsevierStyleHsp" style=""></span>3&#46; The AVERROES study<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> in patients with AF and a VKA contraindication showed a significant impact by apixaban compared to ASA on the annual stroke or systemic embolism rate &#40;1&#46;6&#37; vs 3&#46;6&#37;&#41;&#46; Haemorrhage rates were similar for both treatments&#46; The ROCKET AF study<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">76&#44;77</span></a> demonstrated that rivaroxaban dosed at 20<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>hours is noninferior to warfarin as a means of preventing stroke and peripheral embolism without increasing risk of haemorrhage&#46; Analysis of the treated population found significant differences &#40;1&#46;71&#37; vs 2&#46;16&#37;&#41; with rivaroxaban appearing to be superior&#46; Other anticoagulants currently being developed include edoxaban and betrixaban&#46;</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Antiplatelet drugs</span><p id="par0145" class="elsevierStylePara elsevierViewall">The EAFT study<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a> showed that oral anticoagulants were clearly superior to ASA 300<span class="elsevierStyleHsp" style=""></span>mg for secondary stroke prevention&#46; The ACTIVE-A study showed that 2 antiplatelet drugs used in combination &#40;ASA 75-100<span class="elsevierStyleHsp" style=""></span>mg&#47;CLP 75<span class="elsevierStyleHsp" style=""></span>mg&#41; in patients with a contraindication for VKAs achieved a 28&#37; reduction in risk of stroke compared to ASA alone &#40;75-100<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; However&#44; there was a significant increase in risk of major haemorrhagic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a> In contrast&#44; the ACTIVE W study found oral anticoagulants to be superior to the ASA 75-100<span class="elsevierStyleHsp" style=""></span>mg&#47;CLP 75<span class="elsevierStyleHsp" style=""></span>mg combination for reducing stroke&#44; systemic embolism&#44; AMI&#44; and vascular death&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a></p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Combining oral anticoagulants and antiplatelet drugs</span><p id="par0150" class="elsevierStylePara elsevierViewall">In cases of embolism recurrence despite appropriate anticoagulant treatment&#44; empirical treatment calls for associating these drugs with ASA&#46; Nevertheless&#44; studies have found no differences in stroke or systemic embolism reduction through treatment with warfarin and ASA compared to warfarin alone&#44; whereas the combination is associated with a significant increase in haemorrhagic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> On the other hand&#44; a significant reduction in the risk of death of vascular causes&#44; TIA&#44; non-fatal stroke&#44; and systemic embolism has been observed with the combination of triflusal 600<span class="elsevierStyleHsp" style=""></span>mg&#47;day and moderate-intensity anticoagulants&#44; without a significant increase in haemorrhagic complications&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a> A long-term analysis of one patient subgroup found that the combination of triflusal 600<span class="elsevierStyleHsp" style=""></span>mg&#47;day and an oral anticoagulant was superior to anticoagulant only&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a></p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Antiarrhythmic agents</span><p id="par0155" class="elsevierStylePara elsevierViewall">A post hoc analysis of the ATHENA<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a> study in patients with persistent or paroxysmal AF found that dronedarone reduced risk of stroke by 36&#37; regardless of presence or absence of antithrombotic treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a> Doctors should maintain anticoagulant treatment after stabilising cardiac rhythm in patients with an elevated risk of cardioembolism &#40;CHADS2<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">85</span></a> After cardiac ablation&#44; the AF recurrence rate is 13&#37; at 2 years&#44; 21&#46;8&#37; at 3 years&#44; 35&#37; at 4 years&#44; 46&#46;8&#37; at 5 years&#44; and 54&#46;6&#37; at 6 years&#46; Even patients who do not experience recurrence in the first year cannot be considered cured&#59; follow-up studies show that 40&#37; will experience recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Other drug treatments</span><p id="par0160" class="elsevierStylePara elsevierViewall">Use of statins may prevent either appearance or recurrence of AF&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">87</span></a> Use of ACE inhibitors or ARBs to block the renin-angiotensin system has been shown to reduce the risk of de novo AF&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">88</span></a></p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Non-pharmacological treatments</span><p id="par0165" class="elsevierStylePara elsevierViewall">In most patients with non-valvular AF&#44; thrombi are located in the left atrial appendage&#46; As a result&#44; one possible approach would be excising that structure in selected patients with absolute contraindications to oral anticoagulants&#46; In the PROTECT AF study&#44; percutaneous closure of the atrial appendage was noninferior to warfarin for stroke prevention&#44; although it yielded a higher rate of periprocedural complications&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">89</span></a></p></span></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Other causes of cardioembolism</span><p id="par0170" class="elsevierStylePara elsevierViewall">Evidence regarding risk and recommendations for preventing stroke due to other cardioembolic causes are not as clear as in non-valvular AF or in other specific situations&#46;</p></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Acute myocardial infarction &#40;AMI&#41;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Early onset of heparin treatment followed by oral anticoagulants decreased the risk of IS from 3&#37; to 1&#37; and yielded a &#62;<span class="elsevierStyleHsp" style=""></span>50&#37; reduction in thrombus formation&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> A minimum of 3 months of oral anticoagulant treatment is recommended in anterior AMI with a thrombus detected by an imaging study&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">90</span></a> A meta-analysis comparing oral anticoagulants associated with ASA or used in monotherapy&#44; ASA alone&#44; or placebo found that while warfarin did not reduce mortality or re-infarction rates&#44; it did decrease risk of stroke while also increasing risk of major haemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">91</span></a></p></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Cardiomyopathy with heart failure</span><p id="par0180" class="elsevierStylePara elsevierViewall">In the Warfarin and Antiplatelet Therapy in Chronic Heart Failure trial &#40;WATCH&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">92</span></a> warfarin was associated with a significantly lower stroke rate &#40;0&#46;6&#37;&#41; than ASA dosed at 162<span class="elsevierStyleHsp" style=""></span>mg&#47;day or clopidogrel at 75<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;2&#46;3&#37;&#41;&#46; However&#44; the study&#39;s statistical power is insufficient to establish which treatment is better&#46; Another study&#44; Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction &#40;WARCEF&#41;&#44; is currently underway in patients with LVEF &#8804; 35&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">93</span></a></p></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Rheumatic mitral stenosis</span><p id="par0185" class="elsevierStylePara elsevierViewall">Oral anticoagulant treatment is recommended in patients with mitral stenosis and AF or prior embolism&#44; even when they maintain sinus rhythm&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">94</span></a></p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Mitral valve prolapse</span><p id="par0190" class="elsevierStylePara elsevierViewall">There are no available clinical trials in patients with stroke and mitral valve prolapse&#46; Stroke patients with mitral valve prolapse will require an aetiological study to rule out other possible causes of stroke&#46; If no other causes are identified&#44; antiplatelet treatment is recommended according to general indications for preventing recurrences of stroke of undetermined origin&#46; Oral anticoagulants should be prescribed when patients experience recurrence despite ASA treatment&#44; evidence of prior systemic embolism&#44; or associated AF&#46;</p></span><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Valve replacements</span><p id="par0195" class="elsevierStylePara elsevierViewall">The indication for antithrombotic treatment depends on the type of replacement and associated RFs&#46; As a means of reducing thromboembolic complications&#44; warfarin has been shown to be superior to 2 different antiplatelet regimens &#40;ASA dosed at 650 or 990<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#43; dipyridamole 150-225<span class="elsevierStyleHsp" style=""></span>mg&#47;day or ASA 650<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#43; pentoxifylline 800<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">95</span></a> Oral anticoagulants are indicated for mechanical valves&#59; however&#44; even when INR levels are appropriate &#40;2&#46;5&#8211;3&#46;5&#41;&#44; there is still a yearly risk of thromboembolism of 1-2&#37;&#46; Valves in the mitral position are at more risk than those in the aortic position&#46; INR should therefore remain between 2&#46;5 and 3&#46;5 for mechanical valves in the mitral position&#44; but lower&#44; between 2&#46;0 and 3&#46;0&#44; for bivalvular or Medtronic Hall valves in the aortic position&#44; provided that the factors mentioned above are not present&#46; For biological valves&#44; oral anticoagulants are recommended during the first 3 months after surgery&#44; which is when emboli are most likely to appear &#40;before the valve is completely endothelialised&#41;&#46; Subsequently&#44; doctors may consider long-term antiplatelet therapy with low-dose ASA &#40;75-100<span class="elsevierStyleHsp" style=""></span>mg&#41;&#44; provided that the patient does not have associated RFs such as AF&#44; history of thromboembolism&#44; left ventricular dysfunction&#44; or a hypercoagulable state&#46; Oral anticoagulants are recommended in these cases&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">94</span></a> Associating low doses of ASA &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; or dipyridamole with an oral anticoagulant is more effective for reducing risk of embolism in patients with mechanical valve replacements and stroke recurrence despite appropriate anticoagulant treatment&#46; However&#44; this does significantly increase risk of haemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">96</span></a></p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Patent foramen ovale &#40;PFO&#41; and atrial septal aneurysm &#40;ASA&#41;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Preventive treatment is not indicated for asymptomatic patients with patent foramen ovale&#59; risk of stroke in a patient with PFO resembles that in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">90&#44;97</span></a> If doctors suspect paradoxical embolism due to deep vein thrombosis in a stroke patient with PFO&#44; anticoagulant treatment should be administered for at least 3 months&#46; In other cases&#44; treatment will depend on the risk of recurrence&#44; which is estimated based on co-presence of PFO and other anomalies that are associated with an increased yearly risk of recurrence&#46; Such anomalies include hypercoagulable state or co-presence of an ASA&#59; the significance of the latter is more debatable&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">98&#8211;100</span></a> PICSS&#44; a sub-study of the WARSS clinical trial&#44; observed no differences in recurrence rates among patients with cryptogenic stroke and PFO treated with either aspirin or oral anticoagulants&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">101</span></a> For lack of results from clinical trials on stroke prevention in patients with PFO&#44; antiplatelet treatment is considered appropriate for stroke patients with isolated PFO&#46; Oral anticoagulants are suitable for patients with high-risk PFO or stroke recurrence despite treatment&#46; Results from the CLOSURE-I study<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">102</span></a> show that percutaneous closure of PFO is nonsuperior to medical treatment for stroke prevention&#44; and that its complication rate is higher&#46; The RESPECT and REDUCE trials are still underway&#44; and at present&#44; percutaneous closure of PFO is not recommended except in clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">103</span></a></p></span></span><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0275">Infarcts of rare causes &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;</span><p id="par0205" class="elsevierStylePara elsevierViewall">In this section&#44; we consider only the main aetiologies implicated in IS of rare causes in our setting&#46; These include artery dissection&#44; prothrombotic states&#44; atheromatous plaque in the aortic arch&#44; and lastly&#44; thrombosis of dural sinuses&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0280">Artery dissection</span><p id="par0210" class="elsevierStylePara elsevierViewall">There is no evidence regarding treatment of carotid or extracranial vertebral dissection&#59; analysis of studies performed with either ASA or oral anticoagulants does not reveal significant differences between these regimens&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">104&#8211;106</span></a> A prospective study showed a higher frequency of major haemorrhages with antithrombotic treatment &#40;antiplatelet&#44; 1&#37;&#59; anticoagulant&#44; 2&#37;&#41; than of IS &#40;0&#46;3&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">104</span></a> As efficacy is similar&#44; it would be reasonable to use the drug with the lowest haemorrhagic risk&#44; that is&#44; the antiplatelet drug&#46; Doctors believe that maintaining treatment during 3 to 6 months is appropriate&#44; although no studies support this&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> A systematic review of cases of carotid or vertebral artery dissection treated with angioplasty and stenting concluded that this technique is safe&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">107</span></a> However&#44; no conclusions can be drawn regarding its efficacy&#44; since there are no studies comparing this option to medical treatment&#46;</p></span><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0285">Prothrombotic states</span><p id="par0215" class="elsevierStylePara elsevierViewall">Deep vein thrombosis is an indication for short- or long-term anticoagulation therapy&#44; depending on the clinical and haematological circumstances&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">108</span></a> Although there are guidelines establishing general recommendations for acquired hypercoagulable states&#44; there is no specific evidence regarding secondary stroke prevention&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Oral anticoagulants are recommended in cases of protein C&#44; S&#44; and antithrombin III deficiency&#44; especially in high-risk situations and for secondary prevention&#46; For secondary prevention in patients with lupus anticoagulant&#44; anticoagulant treatment is indicated&#44; although there are no appropriately designed studies that assess the efficacy of that treatment compared to antiplatelet treatment&#46; The APASS study revealed that the presence of antiphospholipid antibodies was not associated with an increased risk of stroke recurrence or with a different response to treatment with ASA 325<span class="elsevierStyleHsp" style=""></span>mg&#47;day or warfarin with an INR of 1&#46;4-2&#46;8&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">109</span></a> Based on these data&#44; aspirin and low-intensity anticoagulation may be considered preventive treatments in patients with antiphospholipid antibody positivity after a first ischaemic stroke&#46; Oral anticoagulants for an INR of 2-3 are recommended for cases of antiphospholipid syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p></span><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0290">Atheromatous plaque in the aortic arch</span><p id="par0220" class="elsevierStylePara elsevierViewall">Atheromatous plaque in the aortic arch is associated with an elevated risk of stroke recurrence and death&#44; especially if plaques measure &#8805;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mm or they are complex &#40;presence of ulceration or mobile components&#41; despite treatment with ASA or oral anticoagulants&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">110&#44;111</span></a> In a retrospective study&#44; use of statins was independently associated with less stroke recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">112</span></a> The Aortic Arch Related Cerebral Hazard Trial &#40;ARCH&#41;&#44; currently underway&#44; compares warfarin to ASA&#47;CLP combination therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">113</span></a> Oral anticoagulants or ASA treatment may be considered to prevent recurrent stroke in patients with ASA and atheromatous plaque in the aortic arch measuring 4<span class="elsevierStyleHsp" style=""></span>mm or larger&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">114</span></a></p></span><span id="sec0235" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0295">Cerebral&#47;dural venous sinus thrombosis</span><p id="par0225" class="elsevierStylePara elsevierViewall">Treatment with oral anticoagulants should be maintained for at least 3 months to avoid rethrombosis following the early-phase anticoagulant treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">115&#44;116</span></a> The decision to extend the treatment over the long term will depend on whether or not a prothrombotic risk factor is detected&#46; If this risk factor is transient&#44; anticoagulants may be discontinued after 3 months&#46; For lower-risk situations&#44; such as protein C or S deficiency&#44; or heterozygosity for factor V Leiden or for the prothrombin G20210A mutation&#44; anticoagulants may be maintained during 6 months&#46; In contrast&#44; for high-risk situations such as antithrombin deficiency&#44; homozygosity for factor V Leiden&#44; or co-presence of 2 or more prothrombotic conditions&#44; long-term anticoagulation is recommended&#46; This is also true in cases of multiple episodes of idiopathic venous thrombosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">117&#44;118</span></a></p></span></span><span id="sec0240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0300">Ischaemic stroke of undetermined origin</span><p id="par0230" class="elsevierStylePara elsevierViewall">In <span class="elsevierStyleItalic">cryptogenic IS</span>&#44; antiplatelet drugs are recommended as the primary treatment method&#46; Some authors recommend anticoagulants when strokes recur despite treatment with antiplatelet drugs&#46; In cases of <span class="elsevierStyleItalic">IS of undetermined aetiology</span> due to an incomplete work-up&#44; missing data must be obtained so as to start the most suitable treatment&#46; For <span class="elsevierStyleItalic">IS of several possible aetiologies</span>&#44; treatment should be tailored to the cause with the highest risk of recurrence and act on all causes where possible&#46;</p></span><span id="sec0245" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0305">Conflicts of interest</span><p id="par0235" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Ischaemic stroke associated with large-vessel arteriosclerosis and small-vessel disease &#40;Table 2&#41;"
          "secciones" => array:5 [
            0 => array:3 [
              "identificador" => "sec0010"
              "titulo" => "Antiplatelet drugs"
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                0 => array:2 [
                  "identificador" => "sec0015"
                  "titulo" => "Acetylsalicylic acid &#40;ASA&#41;"
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                  "titulo" => "SCH 530348"
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              "titulo" => "Associations of antiplatelet drugs"
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                  "titulo" => "ASA and dipyridamole"
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                  "titulo" => "ASA and clopidogrel"
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              "titulo" => "Other combinations"
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              "titulo" => "Oral anticoagulant agents"
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                  "titulo" => "Stenosis of the intracranial arteries"
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                  "titulo" => "Basilar artery stenosis"
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                  "identificador" => "sec0100"
                  "titulo" => "Stroke recurrence despite antiplatelet treatment"
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          "titulo" => "Vascular interventional procedures"
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              "titulo" => "Extracranial carotid artery stenosis"
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                  "titulo" => "Carotid endarterectomy"
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                  "titulo" => "Percutaneous transluminal angioplasty"
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                2 => array:2 [
                  "identificador" => "sec0125"
                  "titulo" => "Extracranial vertebral artery stenosis&#59; subclavian artery stenosis"
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                3 => array:2 [
                  "identificador" => "sec0130"
                  "titulo" => "Intracranial arterial stenosis"
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                4 => array:2 [
                  "identificador" => "sec0135"
                  "titulo" => "Extra-intracranial arterial anastomosis"
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          "identificador" => "sec0140"
          "titulo" => "Ischaemic stroke of cardioembolic origin &#40;Table 3&#41;"
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              "identificador" => "sec0145"
              "titulo" => "Nonvalvular atrial fibrillation"
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                  "identificador" => "sec0150"
                  "titulo" => "Oral anticoagulant agents"
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                  "titulo" => "Antiplatelet drugs"
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                  "identificador" => "sec0160"
                  "titulo" => "Combining oral anticoagulants and antiplatelet drugs"
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                  "identificador" => "sec0165"
                  "titulo" => "Antiarrhythmic agents"
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                  "identificador" => "sec0170"
                  "titulo" => "Other drug treatments"
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                  "titulo" => "Non-pharmacological treatments"
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              "identificador" => "sec0180"
              "titulo" => "Other causes of cardioembolism"
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            2 => array:2 [
              "identificador" => "sec0185"
              "titulo" => "Acute myocardial infarction &#40;AMI&#41;"
            ]
            3 => array:2 [
              "identificador" => "sec0190"
              "titulo" => "Cardiomyopathy with heart failure"
            ]
            4 => array:2 [
              "identificador" => "sec0195"
              "titulo" => "Rheumatic mitral stenosis"
            ]
            5 => array:2 [
              "identificador" => "sec0200"
              "titulo" => "Mitral valve prolapse"
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            6 => array:2 [
              "identificador" => "sec0205"
              "titulo" => "Valve replacements"
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              "identificador" => "sec0210"
              "titulo" => "Patent foramen ovale &#40;PFO&#41; and atrial septal aneurysm &#40;ASA&#41;"
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          "identificador" => "sec0215"
          "titulo" => "Infarcts of rare causes &#40;Table 4&#41;"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0220"
              "titulo" => "Artery dissection"
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            1 => array:2 [
              "identificador" => "sec0225"
              "titulo" => "Prothrombotic states"
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            2 => array:2 [
              "identificador" => "sec0230"
              "titulo" => "Atheromatous plaque in the aortic arch"
            ]
            3 => array:2 [
              "identificador" => "sec0235"
              "titulo" => "Cerebral&#47;dural venous sinus thrombosis"
            ]
          ]
        ]
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          "identificador" => "sec0240"
          "titulo" => "Ischaemic stroke of undetermined origin"
        ]
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          "identificador" => "sec0245"
          "titulo" => "Conflicts of interest"
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          "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0325">Additional References</span>"
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          "titulo" => "References"
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    "fechaRecibido" => "2011-06-09"
    "fechaAceptado" => "2011-06-29"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec309379"
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            0 => "Guidelines"
            1 => "Ischaemic stroke"
            2 => "Transient ischemic attack"
            3 => "Prevention"
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            0 => "Gu&#237;a de pr&#225;ctica cl&#237;nica"
            1 => "Ictus isqu&#233;mico"
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            3 => "Prevenci&#243;n"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To update the <span class="elsevierStyleItalic">ad hoc</span> Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischemic stroke &#40;IS&#41; and Transient Ischaemic Attack &#40;TIA&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype&#46; Levels of evidence and recommendation levels are based on the classi&#64257;cation of the Centre for Evidence-Based Medicine&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In atherothrombotic IS&#44; antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis &#40;70&#8211;99&#37;&#41; reduce the risk of recurrences&#46; In cardioembolic IS &#40;atrial &#64257;brillation&#44; valvular diseases&#44; prosthetic valves and myocardial infarction with mural thrombus&#41; prevention is based on the use of oral anticoagulants&#46; Preventive therapies for uncommon causes of IS will depend on the aetiology&#46; In the case of cerebral venous thrombosis oral anticoagulation is effective&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient&#46;</p>"
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Actualizar las gu&#237;as terap&#233;uticas del Comit&#233; ad hoc del Grupo de Estudio de Enfermedades Cerebrovasculares de la SEN en el tratamiento preventivo de ictus isqu&#233;mico &#40;II&#41; y ataque isqu&#233;mico transitorio &#40;AIT&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Revisi&#243;n de evidencias disponibles sobre la prevenci&#243;n del ictus isqu&#233;mico y AIT en funci&#243;n del subtipo etiol&#243;gico&#46; Los niveles de evidencia y grados de recomendaci&#243;n se han basado en la clasi&#64257;caci&#243;n del Centro de Medicina Basada en la Evidencia&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En el II de origen aterotromb&#243;tico reducen el riesgo de recurrencias el tratamiento antiagregante y los procedimientos revascularizadores en casos seleccionados de estenosis carotidea ipsilateral &#40;70-99&#37;&#41;&#46; La prevenci&#243;n de II de origen cardioemb&#243;lico &#40;&#64257;brilaci&#243;n auricular&#44; valulopat&#237;as&#44; pr&#243;tesis valvulares y en infarto de miocardio con trombo mural&#41; se basa en el uso de anticoagulantes orales&#46; En el II de origen inhabitual&#44; las terapias preventivas depender&#225;n dela etiolog&#237;a&#59; en la trombosis venosa cerebral la anticoagulaci&#243;n oral es e&#64257;caz&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se concluye con recomendaciones de pr&#225;ctica cl&#237;nica en prevenci&#243;n de ictus isqu&#233;mico y AIT adaptadas al subtipo etiol&#243;gico de II que ha presentado el paciente&#46;</p>"
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      0 => array:2 [
        "etiqueta" => "&#9674;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Author affiliations and members of the committee are listed in the <a class="elsevierStyleCrossRef" href="#sec0255">Addendum</a>&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Fuentes B&#44; G&#225;llego J&#44; Gil-Nu&#241;ez A&#44; Morales A&#44; Purroy F&#44; Roquer J&#44; et al&#46; Gu&#237;a para el tratamiento preventivo del ictus isqu&#233;mico y AIT &#40;II&#41;&#46; Recomendaciones seg&#250;n subtipo etiol&#243;gico&#46; Neurolog&#237;a&#46; 2014&#59;29&#58;168&#8211;183&#46;</p>"
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            "apendice" => "<p id="par0245" class="elsevierStylePara elsevierViewall">Ad hoc committee of the SEN Study Group for Cerebrovascular Diseases formed to draw up clinical practice guidelines for stroke&#46;</p> <p id="par0255" class="elsevierStylePara elsevierViewall">Coordinator&#58; Exuperio D&#237;ez-Tejedor&#44; Hospital Universitario La Paz&#44; Madrid&#46;</p>"
            "etiqueta" => "Addendum"
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                "apendice" => "<p id="par0260" class="elsevierStylePara elsevierViewall">Exuperio D&#237;ez-Tejedor &#40;Coord&#41;&#44; Hospital Universitario La Paz&#44; Madrid&#59; Blanca Fuentes &#40;Secretary&#41;&#44; Hospital Universitario La Paz&#44; Madrid&#59; Mar&#237;a Alonso de Leci&#241;ana&#44; Hospital Universitario Ram&#243;n y Cajal&#44; Madrid&#59; Jos&#233; &#193;lvarez-Sabin&#44; Hospital Universitari Vall d&#8217;Hebron&#44; Barcelona&#59; Juan Arenillas&#44; Hospital Universitario Cl&#237;nico de Valladolid&#59; Sergio Calleja&#44; Hospital Universitario Central de Asturias&#44; Oviedo&#59; Ignacio Casado&#44; Hospital San Pedro&#44; C&#225;ceres&#59; Mar Castellanos&#44; Hospital Josep Trueta&#44; Girona&#59; Jos&#233; Castillo&#44; Hospital Cl&#237;nico Universitario&#44; Santiago de Compostela&#59; Antonio D&#225;valos&#44; Hospital Universitari Germans Trias i Pujol&#44; Badalona&#59; Fernando D&#237;az-Otero&#44; Hospital Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#59; Exuperio D&#237;ez-Tejedor&#44; Hospital Universitario La Paz&#44; Madrid&#59; Jos&#233; Antonio Egido&#44; Hospital Cl&#237;nico Universitario San Carlos&#44; Madrid&#59; Juan Carlos Fern&#225;ndez&#44; Hospital Universitario Dr&#46; Negr&#237;n&#44; Las Palmas&#59; Mar Freijo&#44; Hospital Universitario de Basurto&#44; Bilbao&#59; Blanca Fuentes&#44; Hospital Universitario La Paz&#44; Madrid&#59; Jaime G&#225;llego&#44; Hospital General de Navarra&#44; Pamplona&#59; Andr&#233;s Garc&#237;a Pastor&#44; Hospital Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#59; Antonio Gil-N&#250;&#241;ez&#44; Hospital Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#59; Francisco Gilo&#44; Hospital Universitario La Princesa&#44; Madrid&#59; Pablo Irimia&#44; Cl&#237;nica Universitaria de Navarra&#44; Pamplona&#59; Aida Lago&#44; Hospital Universitario La Fe&#44; Valencia&#59; Jos&#233; Maestre&#44; Hospital Universitario Virgen de las Nieves&#44; Granada&#59; Jaime Masjuan&#44; Hospital Universitario Ram&#243;n y Cajal&#44; Madrid&#59; Joan Mart&#237;-F&#225;bregas&#44; Hospital de la Santa Creu i Sant Pau&#44; Barcelona&#59; Patricia Mart&#237;nez-S&#225;nchez&#44; Hospital Universitario La Paz&#44; Madrid&#59; Eduardo Mart&#237;nez-Vila&#44; Cl&#237;nica Universitaria de Navarra&#44; Pamplona&#59; Carlos Molina&#44; Hospital Universitari Vall d&#8217;Hebron&#44; Barcelona&#59; Ana Morales&#44; Hospital Universitario Virgen de la Arrixaca&#44; Murcia&#59; Florentino Nombela&#44; Hospital Universitario La Princesa&#44; Madrid&#59; Francisco Purroy&#44; Hospital Universitario Arnau de Vilanova&#44; L&#233;rida&#59; Marc Rib&#243;&#44; Hospital Universitari Vall d&#8217;Hebron&#44; Barcelona&#59; Manuel Rodr&#237;guez-Y&#225;&#241;ez&#44; Hospital Cl&#237;nico Universitario&#44; Santiago de Compostela&#59; Jaime Roquer&#44; Hospital del Mar&#44; Barcelona&#59; Francisco Rubio&#44; Hospital Universitario de Bellvitge&#44; Barcelona&#59; Tom&#225;s Segura&#44; Hospital Universitario de Albacete&#44; Albacete&#59; Joaqu&#237;n Serena&#44; Hospital Josep Trueta&#44; Gerona&#59; Patricia Simal&#44; Hospital Cl&#237;nico Universitario San Carlos&#44; Madrid&#59; Javier Tejada&#44; Hospital Universitario de Le&#243;n&#44; Le&#243;n&#59; Jos&#233; Vivancos&#44; Hospital Universitario La Princesa&#44; Madrid&#46;</p>"
                "etiqueta" => "A&#46;1"
                "titulo" => "Drafting committee"
                "identificador" => "sec0260"
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                "apendice" => "<p id="par0265" class="elsevierStylePara elsevierViewall">Jos&#233; &#193;lvarez-Sab&#237;n&#44; Hospital Universitari Vall d&#8217;Hebron&#44; Barcelona&#59; Jos&#233; Castillo&#44; Hospital Cl&#237;nico Universitario&#44; Santiago de Compostela&#59; Exuperio D&#237;ez-Tejedor&#44; Hospital Universitario La Paz&#44; Madrid&#59; Antonio Gil-N&#250;&#241;ez&#44; Hospital Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#59; Jos&#233; Larracoechea&#44; Hospital de Cruces&#44; Bilbao&#59; Eduardo Mart&#237;nez-Vila&#44; Cl&#237;nica Universitaria de Navarra&#44; Pamplona&#59; Jaime Masjuan&#44; Hospital Universitario Ram&#243;n y Cajal&#44; Madrid&#59; Jorge Mat&#237;as-Guiu&#44; Hospital Cl&#237;nico Universitario San Carlos&#44; Madrid&#59; Francisco Rubio&#44; Hospital de Bellvitge&#44; Barcelona&#46;</p>"
                "etiqueta" => "A&#46;2"
                "titulo" => "Review or institutional committee"
                "identificador" => "sec0265"
              ]
            ]
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Adapted from the Centre for Evidence Based Medicine &#40;CEBM&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Level of evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Type of study on which classification is based&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Grades of recommendation</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic review of randomised clinical trials &#40;with homogeneity&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B &#40;extrapolation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomised clinical trial with narrow confidence interval&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B &#40;extrapolation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic review of cohort studies &#40;with homogeneity&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C &#40;extrapolation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Individual cohort study &#40;including low-quality randomised clinical trials&#44; e&#46;g&#46; those with a follow-up level below 80&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C &#40;extrapolation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Systematic reviews of case&#8211;control studies &#40;with homogeneity&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C &#40;extrapolation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Case-control studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C &#40;extrapolation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Series of cases or cohort studies or low quality case-control studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D &#40;inconclusive studies&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Experts&#8217; opinion without explicit critical appraisal or based on physiology or pathophysiology&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Levels of evidence and grades of recommendation&#46;</p>"
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      1 => array:7 [
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Level of evidence and recommendation grade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Antiplatelet drugs</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Treatment with antiplatelet drugs is recommended to prevent recurrence&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- ASA &#40;dosed at 50-300<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; reduces the absolute risk of stroke&#44; AMI&#44; or vascular death compared to placebo&#46; It is considered a first-choice drug&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Clopidogrel &#40;75<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; is modestly more effective than ASA for reducing risk of stroke&#44; AMI&#44; and vascular death in patients with atherosclerotic disease&#46; It is considered a first-choice drug&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Triflusal 600<span class="elsevierStyleHsp" style=""></span>mg&#47;day shows similar efficacy to ASA with fewer haemorrhagic complications&#44; and it is considered a first-choice treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- The combination of ASA &#40;25<span class="elsevierStyleHsp" style=""></span>mg&#41; and dipyridamole &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#44; delayed-release&#41; taken twice daily reduces risk of stroke in a similar way to clopidogrel&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- The combination of ASA and clopidogrel is not recommended for preventing stroke due to large-vessel atherosclerosis or small-vessel disease&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Oral anticoagulant agents</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Oral anticoagulants are not recommended for prevention of stroke caused by large vessel atherosclerosis&#44; small vessel disease&#44; or intracranial artery stenosis&#44; except in patients with antiplatelet drug intolerance or contraindications for antiplatelet therapy&#44; or where emboligenic heart disease is also present&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Carotid endarterectomy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Carotid endarterectomy is recommended with ipsilateral carotid stenosis of 70&#37; to 99&#37; and an episode of TIA&#44; amaurosis fugax&#44; or cerebral ischaemia with minor sequelae in the preceding 6 months&#46; Hospitals should have a surgical morbidity and mortality rate of less than 6&#37;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- The procedure may be recommended in patients with 50&#37; to 69&#37; stenosis and men with risk factors and recent hemispheric symptoms&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- This treatment is not appropriate for stenoses of less than 50&#37;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- In cases of TIA or minor stroke&#44; the procedure should be carried out within 2 weeks of the episode&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Percutaneous transluminal carotid angioplasty</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Percutaneous transluminal angioplasty may be indicated as an alternative to carotid endarterectomy in symptomatic cases of carotid stenosis exceeding 50&#37; &#40;arteriography measurement&#41; or &#8805; 70&#37; &#40;non-invasive measurement&#41;&#46; It is especially feasible in patients in whom endarterectomy would be a high-risk or technically difficult procedure&#44; those with restenosis following endarterectomy&#44; stenosis after radiotherapy&#44; or medical contraindications including severe coronary artery disease&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Extra-intracranial anastomosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Extra-intracranial anastomosis is not recommended&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Intracranial endovascular treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Medical treatment&#44; including antiplatelet drugs&#44; statins&#44; and modifying risk factors&#44; is recommended for patients with symptomatic intracranial stenosis&#46; Endovascular treatment is not recommended&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Recommendations&#46; prevention of ischaemic stroke associated with large-vessel arteriosclerosis and small-vessel disease&#46;</p>"
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        "etiqueta" => "Table 3"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Level of evidence and recommendation grade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Non-valvular atrial fibrillation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Primary prevention</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Oral anticoagulants are recommended for patients with non-valvular AF and a high risk of stroke &#40;CHADS &#8805; 2 or CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc &#8805; 1&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Treatment with ASA or oral anticoagulants may be indicated in patients with AF and a low to moderate risk level &#40;CHADS 1 or CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc 1&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Treatment with ASA or no treatment is recommended for patients with AF and a low risk level &#40;CHADS 0 or CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc 0&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Vitamin K antagonists&#44; direct thrombin inhibitors &#40;dabigatran&#41; or factor X inhibitors &#40;rivaroxaban&#44; apixaban&#41; are recommended for patients with an indication for oral anticoagulants&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1a&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- The combination of ASA and clopidogrel may be used in patients with contraindications for oral anticoagulants&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- The combination of ASA and warfarin is not recommended&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Percutaneous left atrial appendage closure may be an alternative to using warfarin to prevent stroke in patients in whom oral anticoagulants are strictly contraindicated&#46; The procedure is associated with higher rates of complications&#44; and should therefore be limited to patients with low complication rates and hospitals with experience&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Secondary prevention</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Oral anticoagulants are recommended for patients with stroke and non-valvular AF &#40;see &#8216;primary prevention&#8217; section and main text&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Acute myocardial infarction &#40;AMI&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Anticoagulant treatment over 3 months&#44; beginning with heparin followed by oral anticoagulants&#44; is recommended for cases of anterior AMI and thrombus detected by imaging techniques&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Sustained treatment with oral anticoagulants after acute myocardial infarction reduces risk of stroke&#44; but increases risk of major haemorrhagic complications&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Cardiomyopathy with heart failure</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- In patients with stroke and heart failure&#44; warfarin treatment is superior to ASA or clopidogrel for reducing risk of stroke&#44; although statistical power is limited&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Rheumatic mitral stenosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Oral anticoagulant treatment is recommended in patients with mitral stenosis who present AF or prior embolism even when they maintain sinus rhythm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Mitral valve prolapse</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- An aetiological study to rule out other possible causes of stroke is crucial in stroke patients with mitral valve prolapse&#46; If no other causes are identified&#44; treatment with antiplatelet drugs is recommended&#44; following general indications for preventing recurrences of stroke of undetermined origin&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Valve replacements</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Oral anticoagulant treatment with warfarin &#40;2&#46;5-3&#46;5 INR&#41; is superior to antiplatelet drugs for reducing thromboembolic complications in patients with mechanical valve replacements&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- For patients with biological valve replacements&#44; oral anticoagulants are recommended during the first 3 months&#44; followed by low-dose ASA as an antiplatelet drug&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Associating ASA 100<span class="elsevierStyleHsp" style=""></span>g&#47;day with an oral anticoagulant delivers better reduction of the risk of embolism in patients with mechanical valve replacements and stroke recurrence despite appropriate anticoagulant treatment&#46; However&#44; this does significantly increase risk of haemorrhage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Anomalies of the interatrial septum</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Preventive treatment is not indicated for asymptomatic patients with patent foramen ovale&#59; risk of stroke in a patient with PFO resembles that in the general population &#40;primary prevention&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- If there is suspicion of paradoxical embolism due to deep vein thrombosis in a stroke patient with PFO&#44; anticoagulant treatment should be administered for at least 3 months&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- In other cases&#44; treatment will depend on risk of recurrence estimated based on the co-presence of PFO and other anomalies associated with elevated risk of recurrence&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- For lack of results from clinical trials on stroke prevention in patients with PFO&#44; antiplatelet treatment is considered appropriate for stroke patients with isolated PFO&#46; Oral anticoagulants are suitable for patients with high-risk PFO or stroke recurrence despite treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Percutaneous closure of a PFO is no better than medical treatment as a means of preventing stroke&#44; and it is associated with more serious complications&#46; The procedure is not recommended&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 1b&#59; Recommendation grade A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Level of evidence and recommendation grade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Artery dissection</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Treatment with ASA over 3 to 6 months is recommended due to being as effective as oral coagulants while causing fewer complications&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2a&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Atheromatous plaque in the aortic arch</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Oral anticoagulants &#40;2&#46;3 INR&#41; or treatment with ASA may be considered to prevent stroke recurrence in patients with cerebral ischaemia and aortic arch atheroma &#8805;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2b&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Use of statins in these patients may reduce risk of stroke recurrence&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Cerebral&#47;dural venous sinus thrombosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Continuing treatment with oral coagulants is recommended during&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Level of evidence 2a&#59; Recommendation grade B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-3 months if the prothrombotic imbalance is transient&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">-6 months for a low-risk case&#58; protein C or S deficiency&#44; heterozygosity for factor V Leiden or for the prothrombin G20210A mutation&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Indefinitely in a high-risk case&#58; antithrombin deficit&#44; homozygosity for factor V Leidenor the co-presence of 2 or more prothrombotic conditions&#44; and in cases of 2 or more episodes of idiopathic venous thrombosis&#46;&nbsp;\t\t\t\t\t\t\n
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            "texto" => "<p id="par0270" class="elsevierStylePara elsevierViewall">Granger CB&#44; Alexander JH&#44; McMurray JJ&#44; Lopes RD&#44; Hylek EM&#44; Hanna M&#44; Al-Khalidi HR&#44; Ansell J&#44; Atar D&#44; Avezum A&#44; Bahit MC&#44; Diaz R&#44; Easton JD&#44; Ezekowitz JA&#44; Flaker G&#44; Garcia D&#44; Geraldes M&#44; Gersh BJ&#44; Golitsyn S&#44; Goto S&#44; Hermosillo AG&#44; Hohnloser SH&#44; Horowitz J&#44; Mohan P&#44; Jansky P&#44; Lewis BS&#44; Lopez-Sendon JL&#44; Pais P&#44; ParkhomenkoA&#44; Verheugt FW&#44; Zhu J&#44; Wallentin L&#59; ARISTOTLE Committees and Investigators&#46;Apixaban versus warfarin in patients with atrial fibrillation&#46; N Engl J Med&#46; 2011 Sep 15&#59;365&#40;11&#41;&#58;981-92&#46;</p> <p id="par0275" class="elsevierStylePara elsevierViewall">Chimowitz MI&#44; Lynn MJ&#44; Derdeyn CP&#44; Turan TN&#44; Fiorella D&#44; Lane BF&#44; Janis LS&#44; Lutsep HL&#44; Barnwell SL&#44; Waters MF&#44; Hoh BL&#44; Hourihane JM&#44; Levy EI&#44; Alexandrov AV&#44; Harrigan MR&#44; Chiu D&#44; Klucznik RP&#44; Clark JM&#44; McDougall CG&#44; Johnson MD&#44; Pride GLJr&#44; Torbey MT&#44; Zaidat OO&#44; Rumboldt Z&#44; Cloft HJ&#59; SAMMPRIS Trial Investigators&#46; Stenting versus aggressive medical therapy for intracranial arterial stenosis&#46; N Engl J Med&#46; 2011 Sep 15&#59;365&#40;11&#41;&#58;993-1003&#46;</p>"
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Article information
ISSN: 21735808
Original language: English
DOI:10.1016/j.nrleng.2011.06.006
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