Stroke prevention in patients with atrial fibrillation and comorbidities: evidence and common sense
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Neth Heart J (2020) 28:501–503 https://doi.org/10.1007/s12471-020-01491-1
Stroke prevention in patients with atrial fibrillation and comorbidities: evidence and common sense J. R. de Groot
Published online: 8 September 2020 © The Author(s) 2020
Patients with atrial fibrillation (AF) are at increased risk of thromboembolic stroke; therefore, the use of oral anticoagulation is recommended for all patients with a CHA2DS2VASc score of 2 or higher (3 or higher for females). Oral anticoagulation should also be considered for patients with a CHA2DS2VASc score of 1 (2 for females) [1]. Indeed, this last group is at a considerably increased risk of stroke as well, indicating that oral anticoagulation is often required, unless there is a good clinical reason to abstain [2]. Possible reasons to reconsider the need for anticoagulation include a perceived high bleeding risk—an increased bleeding risk calls for addressing the risk factors for bleeding, rather than for omitting anticoagulation [1]—or the presence of comorbidities with or without the need for additional antiplatelet therapy. Historically, vitamin K antagonists (VKAs) were the drug of choice for stroke prevention in AF. A metaanalysis of six randomised clinical trials, including a total of 2900 patients using dose-adjusted warfarin, has demonstrated a risk reduction of 64% compared with placebo [3]. Based on these trials, and in the absence of an alternative, VKAs became the drug of choice for stroke prevention in AF across a wide range of patient populations for several decades. With the publication of four large phase 3 trials on the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs, also referred to as direct-acting oral anticoagulants or DOACs), consisting of the thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, a large body of evidence on stroke prevention J. R. de Groot () Department of Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands [email protected]
in AF became available [4–7]. In a meta-analysis of more than 70,000 participants in these randomised studies, DOACs proved to be significantly more efficacious than VKAs, with a 19% reduction in stroke or systemic embolism and a 10% reduction in all-cause mortality compared with warfarin. Furthermore, major bleeding decreased with 14% compared with warfarin, and intracranial bleeding with 52% [8]. The large number of patients included in these trials allowed for numerous post-hoc subanalyses, which shed light on whether the differential efficacy and safety of DOACs compared with VKAs was still present in patients with comorbidities. Such studies may be criticised for being underpowered: the selected populations may not fully reflect clinical reality and the studies are primarily hypothesis generating. Still, one should take into consideration that, for example, the number of patients in the subgroup >75 years of age in the NOAC trials alone exceeds th
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