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Consensus statement
Stroke prevention in patients with arterial hypertension: Recommendations of the Spanish Society of Neurology's Stroke Study Group
Prevención de ictus en pacientes con hipertensión arterial: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología
M. Rodríguez-Yañeza,
,1
, M. Gómez-Chocob,
,1
, E. López-Cancioc, S. Amarod, M. Alonso de Leciñanae, J.F. Arenillasf, O. Ayo-Martíng, M. Castellanosh, M.M. Freijoi, A. García-Pastorj, M. Gomisk, P. Martínez Sánchezl, A. Moralesm, E.J. Palacio-Portillan, J. Roquero, T. Segurag, J. Serenap, J. Vivancos-Moraq, B. Fuentese, ad hoc committee of the Spanish Society of Neurology's Study Group for Cerebrovascular Diseases 1
a Servicio de Neurología, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain
b Servicio de Neurología, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, Spain
c Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain
d Servicio de Neurología, Hospital Clínic i Universitari; Departamento de Medicina, Universidad de Barcelona. Instituto de Investigación Biomédica August Pi i Sunyer (IDIBAPS), Barcelona, Spain
e Servicio de Neurología, Hospital Universitario La Paz, Departamento de Medicina, Universidad Autónoma de Madrid, Área de Neurociencias. Instituto de Investigación IdiPAZ, Madrid, Spain
f Servicio de Neurología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
g Servicio de Neurología, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
h Servicio de Neurología, Complejo Hospitalario Universitario de A Coruña, Instituto de Investigación Biomédica A Coruña, A Coruña, Spain
i Servicio de Neurología, Hospital Universitario Cruces, Biocruces Bizkaia Health Research Institute, Barakaldo, Vizcaya, Spain
j Servicio de Neurología, Hospital Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain
k Servicio de Neurología, Hospital Universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Badalona, Barcelona, Spain
l Servicio de Neurología, Hospital de Torrecárdenas, Almería, Spain
m Servicio de Neurología, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biomédica (IMIB), El Palmar, Murcia, Spain
n Servicio de Neurología, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
o Servicio de Neurología, Hospital del Mar, Barcelona, Spain
p Servicio de Neurología, Biomedical Research Institute of Girona, Hospital Universitario Doctor Josep Trueta, Girona, Spain
q Servicio de Neurología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain
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      "es" => array:1 [
        "titulo" => "Prevenci&#243;n de ictus en pacientes con hipertensi&#243;n arterial&#58; recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Espa&#241;ola de Neurolog&#237;a"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Arterial hypertension is the most prevalent modifiable risk factor for stroke&#44; and one of the most significant factors contributing to the development of the disease&#46; Furthermore&#44; it is associated with greater stroke severity and poorer outcomes&#46; Controlling blood pressure reduces the risk of stroke in primary prevention&#44; but can also reduce the risk of recurrence following a first stroke&#46; In this consensus statement&#44; we review the effect of arterial hypertension on stroke risk and the objectives of blood pressure control both in primary and in secondary stroke prevention&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">We addressed a series of questions identifying practical issues regarding blood pressure management in stroke prevention&#46; We analysed&#58; <span class="elsevierStyleItalic">1&#41;</span> target blood pressure values in primary prevention&#59; <span class="elsevierStyleItalic">2&#41;</span> the most appropriate drugs in primary prevention&#59; <span class="elsevierStyleItalic">3&#41;</span> when to begin antihypertensive treatment after a stroke&#59; <span class="elsevierStyleItalic">4&#41;</span> target blood pressure values in secondary prevention&#59; and <span class="elsevierStyleItalic">5&#41;</span> the most appropriate drugs in secondary prevention&#46; In order to respond to these questions&#44; we conducted a systematic review of the PubMed database and analysed the main clinical trials and meta-analyses&#44; and drafted a series of recommendations&#46; For our recommendation on when to begin antihypertensive treatment&#44; we excluded studies addressing blood pressure management in patients receiving reperfusion therapy&#44; which we considered to be part of acute treatment&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Evidence was classified as level A &#40;high-quality evidence from more than one randomised trial&#44; meta-analyses of high-quality clinical trials&#44; or randomised clinical trial data corroborated by high-quality registry studies&#41;&#44; level B &#40;moderate-quality evidence&#44; based on one or more randomised clinical trials&#59; one or more non-randomised&#44; observational&#44; or high-quality registry studies&#59; meta-analyses of moderate-quality clinical trials&#59; or meta-analyses of non-randomised studies&#41;&#44; or level C &#40;limited evidence&#44; with data from observational studies or registry studies presenting methodological limitations in design or execution&#41;&#46; Grades of recommendation were as follows&#58; class I &#40;strong recommendation&#58; benefits far greater than risk&#41;&#44; class IIa &#40;moderate recommendation&#58; benefit outweighs risk&#41;&#44; class IIb &#40;weak recommendation&#41;&#44; and class III &#40;no benefit&#58; benefit is equal to risk&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Blood pressure management in primary prevention</span><p id="par0020" class="elsevierStylePara elsevierViewall">The definition of arterial hypertension has changed over the years in the light of growing evidence on the effect of blood pressure on vascular risk&#46; While in the 1950s arterial hypertension was defined as systolic blood pressure &#40;SBP&#41;&#8239;&#62;&#8239;180&#8239;mm Hg and diastolic blood pressure &#40;DBP&#41;&#8239;&#62;&#8239;100&#8239;mm Hg&#44; lower values are considered in current definitions&#58; blood pressure is now considered normal when SBP is below 120&#8239;mm Hg and DBP is below 80&#8239;mm Hg&#46; We refer to arterial hypertension in patients with values greater than 130&#47;80&#8239;mm Hg&#44; defining stage 1 hypertension as SBP between 130 and 139&#8239;mm Hg or DBP between 80 and 89&#8239;mm Hg and stage 2 hypertension as SBP&#8239;&#8805;&#8239;140&#8239;mm Hg or DBP&#8239;&#8805;&#8239;90&#8239;mm Hg&#46; SBP values between 120 and 129&#8239;mm Hg are considered high&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Arterial blood pressure values are directly associated with vascular risk&#46; One observational study including a million individuals showed that above 115&#47;75&#8239;mm Hg&#44; every increment of 20&#8239;mm Hg in SBP or 10&#8239;mm Hg in DBP doubled the risk of death due to stroke or ischaemic heart disease&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is also well demonstrated that controlling blood pressure decreases the risk of vascular disease&#46; A meta-analysis conducted in 2016&#44; including over 600 000 patients&#44; demonstrated that every decrease of 10&#8239;mm Hg in SBP was associated with a 20&#37; decrease &#40;relative risk &#91;RR&#93;&#58; 0&#46;80&#59; 95&#37; confidence interval &#91;CI&#93;&#44; 0&#46;77-0&#46;83&#41; in the risk of severe vascular events &#40;acute myocardial infarction&#44; vascular death&#44; coronary revascularisation&#44; stroke&#44; or heart failure&#41;&#44; a 17&#37; decrease in the risk of ischaemic heart disease &#40;RR&#58; 0&#46;83&#59; 95&#37; CI&#44; 0&#46;78-0&#46;88&#41;&#44; a 27&#37; decrease in the risk of ischaemic stroke &#40;RR&#58; 0&#46;73&#59; 95&#37; CI&#44; 0&#46;68-0&#46;77&#41;&#44; and a 13&#37; decrease in all-cause mortality &#40;RR&#58; 0&#46;87&#59; 95&#37; CI&#44; 0&#46;84-0&#46;91&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">While good control of arterial pressure is known to decrease the risk of stroke and other vascular diseases&#44; it is important to establish target values for primary prevention&#44; and to identify which drugs are most effective in reducing blood pressure&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">What are the target blood pressure values in primary prevention&#63;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Various studies have demonstrated that controlling blood pressure reduces the risk of stroke and other vascular diseases in patients with arterial hypertension&#46; In 2014&#44; a meta-analysis analysed individual data from patients included in clinical trials evaluating different antihypertensive drugs against placebo&#44; or comparing intensive blood pressure control strategies against more conservative strategies&#46; The main objective of the study was to analyse the risk of vascular events&#44; defined as stroke&#44; acute myocardial infarction&#44; heart failure&#44; or vascular death&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The meta-analysis included 11 clinical trials with a total of 67 475 participants&#44; who were stratified into 4 groups according to the estimated risk of presenting a vascular event in 5 years&#58; group 1 &#40;&#60; 11&#37;&#41;&#44; group 2 &#40;11&#37;-15&#37;&#41;&#44; group 3 &#40;15&#37;-21&#37;&#41;&#44; and group 4 &#40;&#62; 21&#37;&#41;&#46; Treatment to control blood pressure reduced the relative risk of vascular events in all groups &#40;18&#37; in group 1&#44; 15&#37; in group 2&#44; 13&#37; in group 3&#44; and 15&#37; in group 4&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">While controlling blood pressure is known to be beneficial for reducing vascular risk&#44; target blood pressure values in primary prevention are subject to controversy&#46; The Systolic Hypertension in the Elderly Program &#40;SHEP&#41; study aimed to establish the effect of antihypertensive treatment on stroke risk in primary prevention in patients with SBP&#8239;&#62;&#8239;160&#8239;mm Hg&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> A diuretic &#40;chlortalidone&#41; was compared against placebo&#44; with a follow-up period of 4&#46;5 years&#46; In individuals receiving the diuretic&#44; SBP values decreased to 143&#8239;mm Hg&#44; whereas the placebo group achieved values of 155&#8239;mm Hg&#46; This effect translated to a 36&#37; reduction in the relative risk of stroke in the treatment group&#46; The authors also observed a 27&#37; reduction in the relative risk of acute myocardial infarction and a 13&#37; reduction in the relative risk of all-cause mortality&#46; Another study found that in patients older than 80 years with SBP higher than 160&#8239;mm Hg&#44; the use of indapamide &#40;alone or in combination with perindopril&#41; to reduce blood pressure below 150&#47;80&#8239;mm Hg achieved a 30&#37; reduction in the RR of stroke&#44; a 39&#37; reduction in the RR of fatal stroke&#44; and a 21&#37; reduction in all-cause mortality&#44; compared to placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">A meta-analysis conducted in 2011 aimed to establish the blood pressure values at which antihypertensive treatment should be started&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The study analysed the effect of blood pressure control in a total of 201 566 participants included in 22 clinical trials&#59; participants were grouped according to baseline SBP&#58; &#60; 140&#44; 140-159&#44; 160-179&#44; and &#8805; 180&#8239;mm Hg&#46; All groups achieved a reduction in the relative risk of vascular disease&#58; a 15&#37; reduction in the SBP&#8239;&#60;&#8239;140&#8239;mm Hg group&#44; 18&#37; in the 140-159&#8239;mm Hg group&#44; 20&#37; in the 160-179&#8239;mm Hg group&#44; and 35&#37; in the &#8805; 180&#8239;mm Hg group&#46; The differences between groups in the magnitude of the reduction were not statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239; &#46;17&#41;&#59; use of different cut-off SBP&#47;DBP values also did not identify significant differences&#46; Furthermore&#44; no significant differences were found between groups in the magnitude of the reduction in risk for each mm Hg of reduction in SBP or DBP values&#44; indicating that the benefit was similar in all groups&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The Action to Control Cardiovascular Risk in Diabetes &#40;ACCORD&#41; blood pressure trial compared the effect of intensive and standard blood pressure control &#40;target SBP values &#60; 120&#8239;mm Hg and &#60; 140&#8239;mm Hg&#44; respectively&#41; in patients with diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The study found no significant difference between groups in the primary outcome&#44; a composite of nonfatal myocardial infarction&#44; nonfatal stroke&#44; or cardiovascular death &#40;hazard ratio &#91;HR&#93;&#58; 0&#46;88&#59; 95&#37; CI&#44; 0&#46;73&#8211;1&#46;06&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;20&#41; or for all-cause mortality &#40;HR&#58; 1&#46;07&#59; 95&#37; CI&#44; 0&#46;85&#8211;1&#46;35&#59; <span class="elsevierStyleItalic">P</span> &#61;&#46;55&#41;&#46; However&#44; the authors did report a 41&#37; reduction in the risk of stroke in patients receiving the intensive treatment &#40;HR&#58; 0&#46;59&#59; 95&#37; CI&#44; 0&#46;39&#8211;0&#46;89&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;01&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The Systolic Blood Pressure Intervention Trial &#40;SPRINT&#41; also analysed whether intensive blood pressure control reduces the risk of vascular disease&#59; this study excluded patients with diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The trial included 9361 individuals with high vascular risk&#44; without history of stroke&#44; and with SBP values greater than 130&#8239;mm Hg&#46; Participants were randomly allocated to receive intensive treatment &#40;target SBP&#8239;&#60;&#8239;120&#8239;mm Hg&#41; or standard treatment &#40;target SBP&#8239;&#60;&#8239;140&#8239;mm Hg&#41;&#46; The primary outcome variable was a composite of acute myocardial infarction&#44; coronary disease&#44; stroke&#44; heart failure&#44; and death from cardiovascular causes&#46; This outcome occurred in 1&#46;65&#37; of the intensive treatment group and 2&#46;19&#37; of the standard treatment group&#59; therefore&#44; the intensive treatment reduced risk by 25&#37; &#40;HR&#58; 0&#46;75&#59; 95&#37; CI&#44; 0&#46;64&#8211;0&#46;89&#59; <span class="elsevierStyleItalic">P</span> &#60; &#46;001&#41;&#46; The intensive treatment group also presented a 27&#37; reduction in mortality &#40;HR&#58; 0&#46;73&#59; 95&#37; CI&#44; 0&#46;60&#8211;0&#46;90&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;003&#41;&#46; In the subgroup of participants older than 75 years&#44; the primary outcome variable decreased by 35&#37; and mortality decreased by 33&#37; in the intensive treatment group&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In 2016&#44; a meta-analysis of 16 clinical trials with a total of 52 235 participants analysed the effect of intensive blood pressure control on vascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Globally&#44; the intensive treatment reduced the relative risk of stroke by 29&#37;&#44; ischaemic heart disease by 20&#37;&#44; and vascular death by 21&#37;&#46; However&#44; different studies used different target blood pressure values&#59; therefore&#44; the authors stratified the effect of treatment according to the SBP values achieved&#58; &#60; 130 vs &#8805; 130&#8239;mm Hg&#59; 130-139 vs &#8805; 140&#8239;mm Hg&#59; and 140-149 vs &#8805; 150&#8239;mm Hg&#46; In all groups&#44; intensive treatment achieved a reduction in the risk of stroke&#44; ischaemic heart disease&#44; and vascular death&#46; While no significant differences were observed between groups in the magnitude of the reduction in relative risk&#44; the reduction in absolute risk was smaller in the &#60; 130&#8239;mm Hg group than in the &#8805; 130&#8239;mm Hg group&#44; suggesting that patients with lower initial SBP values present lower vascular risk&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Recommendations&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0070" class="elsevierStylePara elsevierViewall">We recommend starting antihypertensive treatment for primary stroke prevention in patients with blood pressure values greater than 140&#47;90&#8239;mm Hg &#40;class I recommendation&#44; level of evidence A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0075" class="elsevierStylePara elsevierViewall">In patients with arterial hypertension&#44; target blood pressure values should be &#60; 130&#47;80&#8239;mm Hg &#40;class I recommendation&#44; level of evidence A&#41;&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">What are the most appropriate drugs for lowering blood pressure in primary prevention&#63;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Different antihypertensive drugs have been studied in the prevention of vascular events&#44; including diuretics&#44; beta-blockers&#44; angiotensin-converting enzyme &#40;ACE&#41; inhibitors&#44; angiotensin II receptor blockers &#40;ARB&#41;&#44; and calcium channel blockers&#46; The results of the main clinical trials are evaluated in a 2018 meta-analysis comparing different antihypertensive drugs in primary prevention&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Overall&#44; no statistically significant differences were found between drugs with respect to the prevention of acute myocardial infarction or death due to vascular causes&#46; The study only observed a trend towards greater vascular mortality in patients receiving beta-blockers&#44; compared to those using thiazide diuretics &#40;odds ratio &#91;OR&#93;&#58; 1&#46;20&#59; 95&#37; CI&#44; 0&#46;98-1&#46;40&#41; or calcium channel blockers &#40;OR&#58; 1&#46;2&#59; 95&#37; CI&#44; 0&#46;98-1&#46;40&#41;&#46; The specific analysis of stroke risk found that beta-blockers were associated with a 30&#37; increase in the risk of stroke when compared to thiazide diuretics &#40;OR&#58; 1&#46;30&#59; 95&#37; CI&#44; 1&#46;1-1&#46;6&#41;&#44; and a 40&#37; increase when compared to calcium channel blockers &#40;OR&#58; 1&#46;4&#59; 95&#37; CI&#46; 1&#46;1-1&#46;7&#41;&#46; No differences were observed between ACE inhibitors and ARBs and the remaining classes of antihypertensive drugs&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">A recent study aimed to establish when antihypertensive treatment should be administered&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The study included 19 084 patients with arterial hypertension&#44; who were randomly allocated to take an antihypertensive drug either when going to bed or upon waking&#46; The primary outcome variable was vascular risk&#44; defined as vascular death&#44; acute myocardial infarction&#44; coronary revascularisation&#44; heart failure&#44; or stroke&#46; Patients taking the drug at night presented 45&#37; less vascular risk &#40;OR&#58; 0&#46;55&#59; 95&#37; CI&#44; 0&#46;50-0&#46;61&#41;&#46; In the specific analysis of cerebrovascular disease&#44; night-time administration was associated with a 49&#37; reduction in the relative risk of stroke &#40;OR&#58; 0&#46;51&#59; 95&#37; CI&#44; 0&#46;41-0&#46;63&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Recommendations&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1</span><p id="par0095" class="elsevierStylePara elsevierViewall">It is unclear which drugs are the most appropriate for lowering blood pressure in the primary prevention of stroke&#46; As an initial treatment&#44; it is reasonable to use thiazide diuretics and calcium channel blockers rather than beta-blockers &#40;class I recommendation&#44; level of evidence A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2</span><p id="par0100" class="elsevierStylePara elsevierViewall">Taking antihypertensive medications at night may be helpful in reducing the risk of stroke and other vascular diseases &#40;class IIa recommendation&#44; level of evidence B&#41;&#46;</p></li></ul></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Blood pressure management in secondary prevention</span><p id="par0105" class="elsevierStylePara elsevierViewall">Most patients present increased arterial blood pressure during the acute phase of stroke&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> with a subsequent progressive decrease to baseline levels in the following days&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Observational studies have shown that blood pressure values during acute stroke present a U-shaped relationship with stroke outcomes&#58; both the high and low extreme values are associated with poorer functional prognosis&#44; with a higher percentage of early neurological deterioration&#44; stroke recurrence&#44; and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> This effect may be explained by the fact that high blood pressure increases the risk of oedema and haemorrhagic transformation&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> whereas low pressure may reduce perfusion of the ischaemic area&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> It may also be the result of an increase in the inflammatory response &#40;associated with poor prognosis&#41; that is observed during acute stroke in patients with high blood pressure values but no previous diagnosis of arterial hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">These findings raise the question of when antihypertensive treatment should be started after stroke&#44; what target blood pressure values we should establish in secondary prevention of stroke&#44; and whether any specific drug is most appropriate for lowering blood pressure after stroke&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">When should antihypertensive treatment be started after stroke&#63;</span><p id="par0115" class="elsevierStylePara elsevierViewall">With the exception of blood pressure management in the context of reperfusion therapies&#44; most of the data available to answer this question are from studies into the effect of antihypertensive treatment during the first 72&#8239;hours after stroke &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#59; however&#44; some of these studies also include patients with haemorrhagic stroke and a very small percentage of patients who underwent thrombolysis&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">A 2015 meta-analysis of 13 studies assessing the effect of early blood pressure control&#44; including a total of 12 703 patients with acute stroke&#44; found that starting antihypertensive treatment in the first 3 days after the event was not associated with poorer functional outcomes at 3 months &#40;OR&#58; 1&#46;04&#59; 95&#37; CI&#44; 0&#46;96-1&#46;13&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The earliest treatment was reported in the Very Early Nimodipine Use in Stroke &#40;VENUS&#41; trial&#59; in a sample of 454 patients&#44; the study compared a 10-day course of nimopidine against placebo&#44; with treatment onset within 6&#8239;hours of symptom onset&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The authors found no significant differences in functional prognosis at 3 months &#40;RR&#58; 1&#46;2&#59; 95&#37; CI&#44; 0&#46;9-1&#46;6&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The largest studies include the China Antihypertensive Trial in Ischemic Stroke &#40;CATIS&#41; and the Efficacy of Nitric Oxide in Stroke &#40;ENOS&#41; trial&#46; The CATIS trial studied the effect of starting antihypertensive treatment within 48&#8239;hours of symptom onset in a sample of over 4000 patients with acute ischaemic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Globally&#44; starting antihypertensive treatment did not modify functional prognosis at 3 months &#40;OR&#58; 0&#46;99&#59; 95&#37; CI&#44; 0&#46;86-1&#46;15&#41;&#46; However&#44; starting antihypertensive treatment between 24 and 48&#8239;hours was associated with an increased likelihood of good functional prognosis at 3 months &#40;OR&#58; 0&#46;73&#59; 95&#37; CI&#44; 0&#46;55-0&#46;97&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The ENOS study included 4011 patients &#40;3348 with ischaemic stroke&#41;&#44; and also studied the effect of treatment onset within 48&#8239;hours of stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The study compared transdermal glyceryl trinitrate against conventional treatment&#44; finding no differences between treatments in the ordinal analysis of modified Rankin Scale &#40;mRS&#41; scores at 90 days&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The Acute Candesartan Ciletexil Therapy in Stroke Survivors &#40;ACCESS&#41; study compared a 7-day course of candesartan against placebo in patients with ischaemic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Patients were recruited within 36&#8239;hours of treatment onset&#44; and while the trial found no differences in the primary endpoint&#44; dependence at 3 months&#44; it was terminated prematurely when 339 patients had been recruited due to increased prevalence of vascular events &#40;9&#46;8&#37; vs 18&#46;7&#37;&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239; &#46;026&#41; and 12-month mortality &#40;2&#46;9&#37; vs 7&#46;2&#37;&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239; &#46;07&#41; in the placebo group&#46; However&#44; these results were not replicated in the Scandinavian Candesartan Acute Stroke Trial &#40;SCAST&#41;&#44; a subsequent study including 2029 patients &#40;1733 with ischaemic stroke&#41; recruited within 30 hours of symptom onset&#44; which also evaluated the effect of a 7-day course of candesartan against placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> The study was stopped prematurely due to slow recruitment and a lack of funding&#46; This trial used 2 co-primary effect variables&#58; mRS at 6 months and a composite endpoint of vascular death&#44; nonfatal myocardial infarction&#44; and nonfatal stroke at 6 months&#46; Neither variable showed significant differences between groups&#46; Although an ordinal analysis of mRS scores adjusted for age&#44; type of stroke&#44; clinical severity&#44; and SBP showed a trend in favour of placebo&#44; the difference was not statistically significant when 2 co-primary effect variables were used&#46; Among the secondary effect variables&#44; stroke progression was observed in a higher percentage of patients receiving candesartan &#40;6&#37; vs 4&#37;&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239; &#46;04&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The Controlling Hypertension and Hypotension Immediately Post-Stroke &#40;CHHIPS&#41; study randomly allocated 176 patients &#40;99 with ischaemic stroke&#41; to receive a 2-week course of either antihypertensive treatment with labetalol and&#47;or lisinopril&#44; or placebo&#44; starting within 36&#8239;hours of stroke onset&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The primary endpoint&#44; mRS score &#62; 3 at 2 weeks&#44; showed no differences between groups&#59; however&#44; the group receiving antihypertensive treatment showed a lower 90-day mortality rate&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The Prevention Regimen for Effectively Avoiding Second Strokes &#40;PRoFESS&#41; study included a subanalysis comparing telmisartan administered in the first 72&#8239;hours after stroke onset against placebo&#44; finding no difference between groups in functional prognosis at 3 months &#40;OR&#58; 1&#46;03&#59; 95&#37; CI&#44; 0&#46;84-1&#46;26&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The multicentre Continue or Stop Post-Stroke Antihypertensives Collaborative Study &#40;COSSACS&#41; included 763 patients with acute stroke &#40;454 with ischaemic stroke&#41; who were receiving antihypertensive treatment prior to the cerebrovascular event&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> The study evaluated the effect of maintaining or stopping treatment in the first 2 weeks after stroke in patients recruited within 48&#8239;hours of symptom onset&#46; The trial had to be suspended early due to slow recruitment and a lack of funding&#59; however&#44; continuing antihypertensive treatment did not modify the risk of functional dependence at 3 months &#40;RR&#58; 0&#46;86&#59; 95&#37; CI&#44; 0&#46;65&#8211;1&#46;14&#59; <span class="elsevierStyleItalic">P</span> &#61; &#46;30&#41;&#46; The study also found no differences between groups in vascular risk&#44; mortality at 6 months&#44; or number of adverse events&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The Valsartan Efficacy on Modest Blood Pressure Reduction in Acute Ischemic Stroke &#40;VENTURE&#41; study randomly allocated 393 patients with ischaemic stroke to receive a 7-day course of valsartan or placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> The primary outcome variable was mRS score at 90 days&#59; no significant differences were found&#46; However the researchers did observe a higher rate of early neurological deterioration in the valsartan group &#40;OR&#58; 2&#46;43&#59; 95&#37; CI&#44; 1&#46;25-4&#46;73&#41;&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Recommendations&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">1</span><p id="par0170" class="elsevierStylePara elsevierViewall">In patients with ischaemic stroke&#44; antihypertensive treatment should be started after the first 24&#8239;hours following stroke onset &#40;class I recommendation&#44; level of evidence A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">2</span><p id="par0175" class="elsevierStylePara elsevierViewall">Onset of antihypertensive treatment between 24 and 72&#8239;hours after onset is safe and may be appropriate &#40;class I recommendation&#44; level of evidence B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">3</span><p id="par0180" class="elsevierStylePara elsevierViewall">In patients who were receiving antihypertensive treatment prior to stroke&#44; treatment may be resumed between 24 and 48&#8239;hours after stroke onset &#40;class I recommendation&#44; level of evidence B&#41;&#46;</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">What are the target blood pressure values in secondary prevention of stroke&#63;</span><p id="par0185" class="elsevierStylePara elsevierViewall">While various studies have shown that lowering blood pressure reduces the risk of stroke recurrence&#44; it is important to know what blood pressure values should move us to start antihypertensive treatment&#44; and what values we should aim to achieve&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The Perindopril Protection Against Recurrent Stroke Study &#40;PROGRESS&#41; included 6015 patients with or without arterial hypertension who had presented stroke in the previous 5 years and were randomly allocated to receive perindopril with or without indapamide&#44; or placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Mean follow-up time was 3&#46;9 years&#44; and the study&#8217;s primary objective was to analyse stroke recurrence&#46; Globally&#44; antihypertensive treatment reduced the risk of stroke recurrence by 28&#37;&#46; The analysis of patient subgroups defined according to baseline SBP values found that the treatment reduced stroke recurrence in patients with values greater than 140&#8239;mm Hg&#46; For baseline SBP between 120 and 139&#8239;mm Hg&#44; a non-significant trend towards a beneficial effect was observed&#44; and no effect in stroke prevention was observed for patients with values below 120&#8239;mm Hg&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Later studies were included in a meta-analysis published in 2009&#44; which demonstrated that antihypertensive treatment was able to reduce stroke recurrence in patients with SBP greater than 130&#8239;mm Hg &#40;OR&#58; 0&#46;75&#59; 95&#37; CI&#44; 0&#46;62-0&#46;89&#41; and DBP greater than 70&#8239;mm Hg at baseline &#40;OR&#58; 0&#46;64&#59; 95&#37; CI&#44; 0&#46;50-0&#46;80&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> No change in stroke recurrence was observed in patients with baseline SBP below 130&#8239;mm Hg &#40;OR&#58; 0&#46;56&#59; 95&#37; CI&#44; 0&#46;26-1&#46;17&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">However&#44; other studies have shown that the risk of recurrence decreases in line with the blood pressure values&#46; A subanalysis from the PROGRESS trial found that the annual risk of stroke recurrence was 2&#46;23&#37; for achieved follow-up SBP values &#60; 120&#8239;mm Hg&#44; 2&#46;81&#37; for SBP of 120-139&#8239;mm Hg&#44; 3&#46;36&#37; for SBP of 140-159&#8239;mm Hg&#44; and 5&#46;65&#37; for SBP&#8239;&#62;&#8239;160&#8239;mm Hg&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">A meta-analysis published in 2017 also analysed the risk of stroke recurrence as a function of achieved follow-up SBP values&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> The subgroup of patients achieving SBP&#8239;&#60;&#8239;130&#8239;mm Hg presented a lower rate of recurrence &#40;8&#46;3&#37;&#41; than those achieving SBP of 130-140&#8239;mm Hg &#40;9&#46;2&#37;&#41; or &#62; 140&#8239;mm Hg &#40;11&#46;7&#37;&#41;&#59; this difference was statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239; &#46;048&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Other studies have analysed the effect of intensive blood pressure control on the risk of stroke recurrence&#46; The Secondary Prevention of Small Subcortical Strokes &#40;SPS3&#41; study compared intensive blood pressure control &#40;target SBP&#8239;&#60;&#8239;130&#8239;mm Hg&#41; against standard treatment &#40;target SBP 130-149&#8239;mm Hg&#41; in patients with lacunar stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> While no differences were observed in global stroke risk &#40;HR&#58; 0&#46;81&#59; 95&#37; CI&#44; 0&#46;64-1&#46;03&#41;&#44; the intensive control group showed a 63&#37; reduction in the risk of brain haemorrhage &#40;OR&#58; 0&#46;37&#59; 95&#37; CI&#44; 0&#46;15-0&#46;95&#41;&#46; The Recurrent Stroke Prevention Clinical Outcome &#40;RESPECT&#41; study was published recently&#59; the study included 1280 patients who had presented a stroke in the previous 3 years&#44; who were randomly allocated to receive either intensive blood pressure control &#40;target &#60; 120&#47;80&#8239;mm Hg&#41; or standard treatment &#40;140&#47;90&#8239;mm Hg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The intensive treatment was not associated with a decrease in the risk of stroke &#40;OR&#58; 0&#46;73&#59; 95&#37; CI&#44; 0&#46;49-1&#46;11&#41;&#44; ischaemic heart disease &#40;OR&#58; 1&#46;23&#59; 95&#37; CI&#44; 0&#46;33-4&#46;59&#41;&#44; or mortality &#40;OR&#58; 0&#46;80&#59; 95&#37; CI&#44; 0&#46;49-1&#46;29&#41;&#44; but was associated with a considerable reduction in the risk of brain haemorrhage &#40;OR&#58; 0&#46;09&#59; 95&#37; CI&#44; 0&#46;01-0&#46;70&#41;&#46; The data from this study were included in a subsequent meta-analysis that found that the intensive treatment reduced the relative risk of stroke recurrence by 22&#37; &#40;OR&#58; 0&#46;78&#59; 95&#37; CI&#44; 0&#46;64-0&#46;96&#41;&#44; with target blood pressure values &#60;130&#47;80&#8239;mm Hg being associated with the greatest benefit&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Recommendations&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">1</span><p id="par0220" class="elsevierStylePara elsevierViewall">In secondary prevention of stroke&#44; antihypertensive treatment should aim to achieve blood pressure values &#60; 130&#47;80&#8239;mm Hg &#40;class I recommendation&#44; level of evidence B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">2</span><p id="par0225" class="elsevierStylePara elsevierViewall">We recommend starting antihypertensive treatment in patients with ischaemic stroke who persistently present blood pressure values greater than 140&#47;90&#8239;mm Hg &#40;class I recommendation&#44; level of evidence A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">3</span><p id="par0230" class="elsevierStylePara elsevierViewall">In patients with lacunar stroke&#44; treatment should be started if blood pressure values are higher than 130&#47;80&#8239;mm Hg &#40;class I recommendation&#44; level of evidence B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">4</span><p id="par0235" class="elsevierStylePara elsevierViewall">Patients with stroke who present blood pressure values above 140&#47;90&#8239;mm Hg may benefit from antihypertensive treatment &#40;class IIb recommendation&#44; level of evidence B&#41;&#46;</p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">What are the most appropriate drugs for lowering blood pressure in secondary prevention&#63;</span><p id="par0240" class="elsevierStylePara elsevierViewall">Several studies have employed different drugs in secondary prevention of stroke&#44; including ACE inhibitors&#44; ARBs&#44; beta-blockers&#44; and calcium channel blockers &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The Post-stroke Antihypertensive Treatment Study &#40;PATS&#41; was the first study to demonstrate that the diuretic indapamide reduces the relative risk of stroke by 29&#37;&#44; compared to placebo&#44; in patients with stroke or transient ischaemic attack&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0245" class="elsevierStylePara elsevierViewall">Subsequent studies have also shown that diuretics are beneficial in reducing the risk of stroke recurrence&#46; The PROGRESS study included 6015 patients who had presented stroke or transient ischaemic attack in the last 5 years&#44; who were randomly allocated to receive perindopril&#44; perindopril&#8239;&#43;&#8239;indapamide&#44; or placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Compared to placebo&#44; the group receiving perindopril only did not show reduced risk of stroke recurrence &#40;OR&#58; 0&#46;95&#59; 95&#37; CI&#44; 0&#46;77-1&#46;19&#41;&#59; however&#44; combination therapy with indapamide achieved a 43&#37; reduction in the relative risk of stroke recurrence &#40;OR&#58; 0&#46;57&#59; 95&#37; CI&#44; 0&#46;46-0&#46;70&#41;&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The Morbidity and Mortality after Stroke&#44; Eprosartan Compared with Nitrendipine for Secondary Prevention &#40;MOSES&#41; study compared an ARB &#40;eprosartan&#41; and a calcium channel blocker &#40;nitrendipine&#41; in patients presenting stroke in the previous 2 years&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> While both groups achieved similar blood pressure values &#40;137&#46;5&#47;80&#46;8&#8239;mm Hg vs 136&#46;0&#47;80&#46;2&#8239;mm Hg&#41;&#44; patients receiving eprosartan presented 25&#37; less relative risk of stroke recurrence &#40;OR&#58; 0&#46;75&#59; 95&#37; CI&#44; 0&#46;58-0&#46;97&#41;&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Recommendations&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0260" class="elsevierStylePara elsevierViewall">We recommend using either an ARB or a diuretic&#44; either alone or in combination with an ACE inhibitor&#44; as an initial treatment in the secondary prevention of stroke &#40;class I recommendation&#44; level of evidence B&#41;&#46; However&#44; insufficient data are available to compare different antihypertensive drugs in secondary stroke prevention&#46;</p></li></ul></p></span></span></span>"
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          "identificador" => "xpalclavsec1396218"
          "palabras" => array:4 [
            0 => "Ictus"
            1 => "Prevenci&#243;n"
            2 => "Presi&#243;n arterial"
            3 => "F&#225;rmacos antihipertensivos"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To update the recommendations of the Spanish Society of Neurology on primary and secondary stroke prevention in patients with arterial hypertension&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Development</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We proposed several questions to identify practical issues for the management of blood pressure &#40;BP&#41; in stroke prevention&#44; analysing the objectives of blood pressure control&#44; which drugs are most appropriate in primary prevention&#44; when antihypertensive treatment should be started after a stroke&#44; what levels we should aim to achieve&#44; and which drugs are most appropriate in secondary stroke prevention&#46; We conducted a systematic review of the PubMed database and analysed the main clinical trials to address these questions and establish a series of recommendations&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conclusions</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">In primary stroke prevention&#44; antihypertensive treatment should be started in patients with BP levels&#8239;&#62;&#8239; 140&#47;90&#8239;mmHg&#44; with a target BP of &#60; 130&#47;80&#8239;mmHg&#46; In secondary stroke prevention&#44; we recommend starting antihypertensive treatment after the acute phase &#40;first 24&#8239;hours&#41;&#44; with a target BP of &#60; 130&#47;80&#8239;mmHg&#46; The use of angiotensin-II receptor antagonists or diuretics alone or in combination with angiotensin-converting enzyme inhibitors is preferable&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Development"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Objetivo</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Actualizar las recomendaciones de la Sociedad Espa&#241;ola de Neurolog&#237;a para la prevenci&#243;n de ictus&#44; tanto primaria como secundaria&#44; en pacientes con hipertensi&#243;n arterial&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Desarrollo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se han planteado diferentes preguntas para identificar cuestiones pr&#225;cticas para el manejo de la presi&#243;n arterial &#40;PA&#41; en prevenci&#243;n de ictus&#44; analizando cu&#225;l debe ser el objetivo de control de la presi&#243;n arterial y cu&#225;les son los f&#225;rmacos m&#225;s adecuados en prevenci&#243;n primaria&#44; cu&#225;ndo iniciar el tratamiento antihipertensivo despu&#233;s de un ictus&#44; cu&#225;les son las cifras que debemos alcanzar y qu&#233; f&#225;rmacos son los m&#225;s adecuados en prevenci&#243;n secundaria de ictus&#46; Se ha realizado una revisi&#243;n sistem&#225;tica en Pubmed analizando los principales ensayos cl&#237;nicos para dar respuesta a estas preguntas y se han elaborado unas recomendaciones&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En prevenci&#243;n primaria se recomienda iniciar tratamiento antihipertensivo con cifras de PA&#8239;&#62;&#8239;140&#47;90&#8239;mmHg&#44; con un objetivo de control de PA&#8239;&#60;&#8239;130&#47;80&#8239;mmHg&#46; En prevenci&#243;n secundaria de ictus se recomienda iniciar tratamiento antihipertensivo pasada la fase aguda &#40;primeras 24&#8239;h&#41; con un objetivo de control de PA&#8239;&#60;&#8239;130&#47;80&#8239;mmHg&#44; siendo preferible el empleo de ARA-II o diur&#233;ticos solos o en combinaci&#243;n con IECA&#46;</p></span>"
        "secciones" => array:3 [
          0 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Desarrollo"
          ]
          2 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Both of these authors are the lead authors&#46;</p>"
        "identificador" => "fn0005"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rodr&#237;guez-Ya&#241;ez M&#44; G&#243;mez-Choco M&#44; L&#243;pez-Cancio E&#44; Amaro S&#44; Alonso de Leci&#241;ana M&#44; Arenillas JF&#44; et al&#46; Prevenci&#243;n de ictus en pacientes con hipertensi&#243;n arterial&#58; recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Espa&#241;ola de Neurolog&#237;a&#46; Neurolog&#237;a&#46; 2021&#59;36&#58;462&#8211;471&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">BI&#58; Barthel Index&#59; CI&#58; confidence interval&#59; GTN&#58; glyceryl trinitrate&#59; HR&#58; hazard ratio&#59; mRS&#58; modified Rankin Scale&#59; NA&#58; not available&#59; OR&#58; odds ratio&#59; RR&#58; relative risk&#46;</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"><th 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" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">No&#46; patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Time window for study inclusion&#44; hours&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Time from symptom onset&#44; hours &#40;mean&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">&#37; tPA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Intervention&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VENUS<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">454 &#40;261 ischaemic stroke&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 6</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nimodipine vs placebo&#44; 10 days</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">mRS &#62; 3 at 3 months&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">Overall&#58; RR&#58; 1&#46;2 &#40;95&#37; CI&#44; 0&#46;9-1&#46;6&#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">Ischaemic&#58; RR&#58; 1&#46;4 &#40;95&#37; CI&#44; 1-2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACCESS<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2003</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">339 ischaemic stroke</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 36</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;mean&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Candesartan vs placebo&#44; 7 days</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">BI at 3 months&#58; no differences&#46;&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">Study stopped early due to increased vascular events and mortality at 12 months in the placebo group&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">OR&#58; 0&#46;48 &#40;95&#37; CI&#44; 0&#46;25-0&#46;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRoFESS<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></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">2009&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">1360 ischaemic stroke&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">&#60; 72&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">58 &#40;mean&#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">NA&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">Telmisartan vs placebo&#44; 90 days&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">mRS at 30 days&#58; no differences in ordinal analysis &#40;OR&#58; 1&#46;03&#59; 95&#37; CI&#44; 0&#46;84-1&#46;26&#41; or binary analysis &#40;OR&#58; 1 &#40;95&#37; CI&#44; 0&#46;77-1&#46;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CHHIPS<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2009</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">176 &#40;99 ischaemic stroke&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 36</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Labetalol or lisinopril vs placebo&#44; 2 weeks</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">mRS &#62; 3 at 2 weeks&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">RR&#58; 1&#46;03 &#40;95&#37; CI&#44; 0&#46;8-1&#46;33&#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">Reduced 90-day mortality in treatment group &#40;HR&#58; 0&#46;4 &#40;95&#37; CI&#44; 0&#46;2-1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">COSSACS<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2010</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">763 &#40;454 ischaemic stroke&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 48</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maintaining or suspending antihypertensive treatment for 2 weeks</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">mRS &#62; 3 at 2 weeks&#46;&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">Overall&#58; RR&#58; 0&#46;86 &#40;95&#37; CI&#44; 0&#46;65-1&#46;14&#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">Ischaemic stroke RR&#58; 0&#46;70 &#40;95&#37; CI&#44; 0&#46;51-0&#46;99&#59; P&#8239;&#61;&#8239; &#46;045&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SCAST<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2011</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2029 &#40;1733 ischaemic stroke&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 30</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;7</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Candesartan vs placebo&#44; 7 days</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">mRS &#62; 2 at 6 months OR&#58; 1&#46;13 &#40;95&#37; CI&#44; 0&#46;97-1&#46;32&#59; adjusted&#58; 1&#46;17&#59; 95&#37; CI&#44; 1-1&#46;38&#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">Vascular death&#44; nonfatal myocardial infarction&#44; or nonfatal stroke at 6 months &#40;HR&#58; 1&#46;09 &#91;95&#37; CI&#44; 0&#46;84-1&#46;41&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CATIS<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4071 ischaemic stroke</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 48</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;mean&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Administration or non-administration of antihypertensive drugs during hospitalisation</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">mRS &#62; 2 at 14 days or at discharge&#46;&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">Overall&#58; OR&#58; 1 &#40;95&#37; CI&#44; 0&#46;88-1&#46;14&#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">Treatment onset &#62; 24&#8239;hours&#58; OR&#58; 0&#46;73 &#40;95&#37; CI&#44; 0&#46;55-0&#46;97&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VENTURE<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">393</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 48</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;mean&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Valsartan or no treatment&#44; 7 days</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">mRS &#62; 2 at 90 days&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">OR&#58; 1&#46;1 &#40;95&#37; CI&#44; 0&#46;69-1&#46;79&#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">Higher percentage of early neurological deterioration in the valsartan group&#46; OR&#58; 2&#46;43 &#40;95&#37; CI&#44; 1&#46;25-4&#46;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ENOS<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4011 &#40;3348 ischaemic stroke&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 48</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;median&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;6</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Transdermal GTN vs no GTN&#44; 7 days</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">mRS at 90 days&#44; ordinal&#58;&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">OR&#58; 1&#46;01 &#40;95&#37; CI&#44; 0&#46;91-1&#46;13&#41;&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"><th 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" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">No&#46; patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Study groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Mean follow-up time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Target blood pressure values achieved&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Reduction in stroke risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PATS<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1995</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5665</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">1&#46; Placebo&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 years</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">1&#46; Placebo&#58; 149&#47;87&#8239;mm Hg&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#37; in favour of indapamide</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OR&#58; 0&#46;71&#59; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;0009</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">2&#46; Indapamide&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">2&#46; Indapamide&#58; 144&#47;89&#8239;mm Hg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PROGRESS<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2001</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6015</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">1&#46; Placebo&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;9 years</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">1&#46; Perindopril&#58; decrease of 4&#46;4-5&#46;7&#8239;mm Hg with respect to placebo&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  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#37; in favour of perindopril&#8239;&#43;&#8239;indapamide</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">1&#46; Perindopril vs placebo&#58; OR&#58; 0&#46;95 &#40;95&#37; CI&#58; 0&#46;77-1&#46;19&#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">2&#46; Perindopril&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; Perindopril&#8239;&#43;&#8239;indapamide&#58; decrease of 9&#46;3-14&#46;2&#8239;mm Hg with respect to placebo</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; Perindopril&#8239;&#43;&#8239;indapamide vs placebo&#58; OR&#58; 0&#46;57 &#40;95&#37; CI&#58; 0&#46;46-0&#46;70&#41;</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">3&#46; Perindopril&#8239;&#43;&#8239;indapamide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
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                  \t\t\t\t">MOSES<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2005</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1405</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">1&#46; Eprosartan&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;5 years</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">1&#46; Eprosartan&#58; 137&#46;5&#47;80&#46;8&#8239;mm Hg&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37; in favour of eprosartan</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OR&#58; 0&#46;75 &#40;95&#37; CI&#58; 0&#46;58-0&#46;97&#41;</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">2&#46; Nitrendipine&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">2&#46; Nitrendipine&#58; 136&#46;0&#47;80&#46;2&#8239;mm Hg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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ISSN: 21735808
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es en pt

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