Cerebrovascular and Bleeding Outcomes of Warfarin versus Direct Oral Anticoagulants Therapy for Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objectives: To compare the effects on cerebral health in atrial fibrillation patients receiving either warfarin or direct oral anticoagulants (DOACs). Atrial fibrillation is linked to a higher likelihood of both stroke and cognitive impairment. While warfarin has historically served as the leading anticoagulant treatment, DOACs are now more frequently viewed as alternatives with an improved safety profile. Methods: The methodology involved an extensive search of multiple databases, completed up to June 2024. This search yielded randomized controlled trials, which together enrolled over 60,000 participants between the ages of 70 and 84. The DOACs studied were dabigatran, rivaroxaban, apixaban, and edoxaban, given in various dosages. Warfarin was administered with dose adjustments to keep the international normalized ratio within a target range of 2.0 to 3.0. Results: With a relative risk of 0.81 (95% CI, p < 0.00001; I2 = 19%), the results showed that 20 high-dose DOACs considerably decreased the risk of stroke when compared to warfarin. However, there were no discernible variations for major bleeding (relative risk 0.89), moderate bleeding (relative risk 0.92), or cardiovascular events (relative risk 0.96). Conclusion: The DOACs are frequently more efficacious than warfarin in avoiding stroke and systemic embolism in patients with non-valvular atrial fibrillation. A significant decline in hemorrhagic stroke was the main cause of the pooled data's 19% relative risk reduction in stroke or systemic embolism. While bleeding outcomes varied among the individual DOACs, the overall findings support their favorable risk-benefit profile. Compared to warfarin, DOACs consistently showed fewer intracranial hemorrhages and a more favorable bleeding profile. These results support prioritizing DOACs in clinical practice, given their enhanced safety and reduced mortality rates. However, due to differences in bleeding risks among DOACs, treatment decisions should be tailored to individual patient factors.