Direct oral anticoagulants (DOAC) for patients with atrial fibrillation during the COVID-19 pandemic

Dear Editor,

We compliment Gómez et al.¹ for reporting their large retrospective, multicenter, nationwide study that investigated the risk factors associated with mortality and poor prognosis in patients with coronavirus disease 2019 (COVID-19) and concurrent atrial fibrillation. In the study, it has been found in the multivariable analysis that the use of direct oral anticoagulants (DOACs) in patients with COVID-19 and atrial fibrillation was associated with significantly reduced risk of mortality (odds ratio = 0.597; 95% confidence interval 0.402–0.888). The findings of this study resonate with the findings of a meta-analysis² which determined the effects of the use of DOACs on morbidity and mortality in patients with COVID-19, and reported that the use of DOACs was significantly associated with a reduced risk of severe or fatal COVID-19 (odds ratio = 0.50; 95% confidence interval 0.33–0.76).

We believe there are implications from the findings where the authors did not discuss in their article.¹ Firstly, the mortality benefits with DOACs suggest their potential antiviral activity against SARS-CoV-2, the causative pathogen of COVID-19. DOACs, particularly the direct FXa inhibitors, may prevent coronavirus entry into human cells by inhibiting the cleavage of the spike protein of SARS-CoV-2 into the S1 and S2 subunits, which can serve to facilitate the fusion of the virus with the host cell membrane.³ Secondly, the association between the use of DOACs and reduced risk of mortality may be attributable to their anti-inflammatory activities. Previously, a post hoc analysis of the X-VeRT trial⁴ reported that the use of rivaroxaban led to a significant reduction in the levels of D-dimer and interleukin-6 in patients with atrial fibrillation, where both of which have been associated with COVID-19 mortality. These results indicate that DOACs may also inhibit the excessive immune response and cytokine storm involved in the pathophysiology of COVID-19. Thirdly, the positive findings should encourage more widespread prescribing of DOACs for patients with atrial fibrillation who are indicated for long-term anticoagulation during the COVID-19 pandemic. Due to COVID-19 related movement restrictions, it has been previously suggested that patients who are newly diagnosed with atrial fibrillation and require anticoagulant treatment as well as patients with atrial fibrillation receiving vitamin K antagonists, should be prescribed/switched to DOACs during the COVID-19 pandemic.⁵ This is owing to the ease of monitoring with the use of DOACs compared to vitamin K antagonists. The findings of the study thus provide another rationale to prescribe DOACs for patients with atrial fibrillation who require anticoagulation during the COVID-19 pandemic, in order to reduce the risk of mortality, shall they acquire COVID-19. In fact, the presence of atrial fibrillation significantly increases the risk of serious complications and death from COVID-19.

Taken together, we urge clinicians to take the findings of this study¹ into consideration when deciding anticoagulant treatment in patients with atrial fibrillation during the COVID-19 pandemic.

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

All authors declare that they have no potential conflicts of interest that might be relevant to the contents of this article.