Journal of Clinical Trials
Open Access

Abstract

Atrial fibrillation, Stroke and the Use of Novel Oral Anticoagulants: A Review of Phase III Randomized Clinical Trials

Ahmad Saleh Malkawi*, Azhar Malkawi and Nasr Alrabadi

Atrial Fibrillation (AF) significantly increases the risk of stroke, a leading cause of death and disability. Anticoagulation therapy, traditionally with warfarin, effectively reduces stroke risk but is limited by the need for frequent monitoring to maintain therapeutic international normalized ratio (INR). Novel Anticoagulants (NOVACs), including Direct Thrombin Inhibitors (DTIs) and Direct Factor Xa Inhibitors (DFXaIs), have emerged as promising alternatives. This review examines phase III Randomized Clinical Trials (RCTs) assessing NOVACs for stroke prevention in AF patients compared to warfarin. The RE-LY trial evaluated dabigatran, finding that a low dose (110 mg twice daily) had comparable efficacy to warfarin in reducing stroke and systemic embolism but with a lower risk of major hemorrhage. A higher dose (150 mg twice daily) showed superior efficacy in reducing stroke and systemic embolism but had similar bleeding rates. The ROCKET-AF trial found rivaroxaban (20 mg once daily) comparable to warfarin for stroke prevention and major hemorrhage risk. The ARISTOTLE trial demonstrated that apixaban was superior to warfarin in reducing both stroke/systemic embolism and major bleeding events. Overall, NOVACs offer at least comparable safety and efficacy profiles to warfarin and may be preferred when monitoring anticoagulation effects is impractical. While NOVACs demonstrate promise, generalized phase IV RCTs are recommended to compare their long-term safety and efficacy, with warfarin remaining a benchmark for stroke prevention in AF.

Published Date: 2025-03-07; Received Date: 2025-02-06