Direct oral anticoagulants vs. warfarin in patients with atrial fibrillation: A meta-analysis

By Samar Mahmoud, MS
Published January 26, 2022

Key Takeaways

  • This large meta-analysis found that in patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) showed more favorable safety and efficacy profiles when compared with warfarin. 

Previous studies have reported that DOACs, compared with warfarin, are associated with decreased risk of stroke and major bleeding events in patients with AF.

Why This Study Matters

This study performed a meta-analysis using individual patient data, which offers many advantages over traditional study-level data, to determine efficacy and safety outcomes for DOACs in comparison to warfarin.

Study Design

This study included patients from the COMBINE AF database, which consists of all participants in 4 clinical trials comparing DOACs to warfarin (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48). 

There were a total of 71,683 patients included in the study, with 29,362 receiving a standard dose of DOAC, 13,049 recieving a lower dose of DOAC, and 29,272 on warfarin. Investigators calculated hazard ratios for efficacy and safety outcomes. 

Results and Conclusions

Standard-dose DOACs were associated with a lower risk of stroke, death, and intracranial bleeding in comparison to warfarin. However, investigators did not identify a statistically different hazard of major bleeding when comparing standard-dose DOACs to warfarin. 

Lower-dose DOACs were associated with a lower hazard of intracranial bleeding, death, and major bleeding, but not stroke and systemic embolism.  While the treatment effects observed for standard and lower-dose DOACs versus warfarin were consistent across age and gender for stroke and death, treatment with standard-dose DOACs was favored in patients without a history of vitamin K antagonist use and lower creatinine clearance. 

For major bleeding, standard-dose DOACs were the preferred treatment of choice for patients with lower body weight. Standard and lower-dose DOACs led to greater treatment benefits for younger patients than warfarin. 

Related Research

Consider these findings from similar research studies:

  • Valvular atrial fibrillation patients treated with DOACs were at lower risk for stroke and major bleeding in comparison to those treated with warfarin (Source). 

  • DOACs are an effective and safe option for patients with atrial fibrillation who have had an ischemic stroke (Source).

Original Source 

Carnicelli AP, Hong H, Connolly SJ, et al. Direct oral anticoagulants versus warfarin in patients with atrial fibrillation: patient-level network meta-analyses of randomized clinical trials with interaction testing by age and sex. Circulation. Published online January 5, 2022:CIRCULATIONAHA.121.056355.

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