Improving Patient Outcomes in Preventing Atrial Fibrillation-related Stroke with Non-Vitamin K Antagonist Oral Anticoagulants

Abstract

The rising incidence of atrial fibrillation (AF) is increasingly resulting in a substantial worldwide increase in AF-related stroke, particularly in elderly patients and this is creating an increasingly serious healthcare burden. Guidelines recommend the use of AF-related stroke prophylaxis but adherence to these remains poor. Studies conducted in the 1990s showed that warfarin reduced the risk of AF-related stroke by an overall 64% compared with placebo. Subsequently, prophylactic treatment was further improved with the development of non-vitamin K antagonist oral anticoagulants (NOACs). More recently, a meta-analysis of four large clinical trials on NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) showed there was a relative risk reduction of 0.81 (p<0.0001) favouring NOAC treatment over warfarin for stroke or systemic embolic events in patients with AF. The largest trial of NOACs in AF-related stroke, to date, was the ENGAGE AF-TIMI 48 study (n=21,105) which showed that edoxaban was non-inferior to warfarin for ischaemic stroke reduction but significantly reduced bleeding and cardiovascular mortality. A recent subgroup analysis of this study showed that with edoxaban the incidences of intracranial haemorrhage (ICH) subtypes (all ICH, fatal ICH, fatal, subdural and epidural bleed) were significantly lower with 60 mg of edoxaban (p=0.013–<0.001). Edoxaban was also shown to be an effective option in patients with prior stroke. In addition, edoxaban was shown to reduce deaths due to fatal bleeds compared with warfarin. The results of current studies, especially the ENGAGE AF-TIMI 48 subgroup analysis therefore, show that the benefits of anticoagulation therapy in patients with AF substantially outweigh the risks.