A systematic review and meta-analysis published in The BMJ evaluated the safety, efficacy, and cost-effectiveness of direct acting oral anticoagulants (DOACs) for the prevention of stroke among patients with atrial fibrillation (AF).

Study authors searched Medline, PreMedline, Embase, and The Cochrane Library for published randomized trials assessing the use of a DOAC, vitamin K antagonist, or antiplatelet for stroke prevention in AF patients. A total of 23 randomized trials (n=94,656) were included for analysis. Thirteen of these studies compared DOAC with warfarin dosed to achieve a target INR 2.0 to 3.0. 

The greatest risk reduction of stroke or systemic embolism was seen with dabigatran 150mg twice daily (odds ratio [OR] 0.65, 95% CI: 0.52-0.81), followed by apixaban 5mg twice daily (OR 0.79, 95% CI: 0.66-0.94), edoxaban 60mg once daily (OR 0.86, 95% CI: 0.74-1.01), and rivaroxaban 20mg once daily (OR 0.88, 955 CI: 0.74-1.03), when compared with warfarin. 

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Edoxaban 60mg once daily (OR 1.33, 95% CI: 1.02-1.75) and rivaroxaban 20mg once daily (OR 1.35, 95% CI: 1.03-1.78) were associated with higher risks of stroke or systemic embolism vs. dabigatran 150mg twice daily. 

All DOACs exhibited a lower risk of all-cause mortality vs. warfarin, the authors noted.

Compared to warfarin, the risk of major bleeding was lower with DOACs: apixaban 5mg twice daily (OR 0.71, 95% IC: 0.61-0.81), dabigatran 110mg twice daily  (OR 0.80, 95% CI: 0.69-0.93), edoxaban 30mg once daily (OR 0.46, 95% CI: 0.40-0.54), and edoxaban 60mg once daily (OR 0.78, 95% CI: 0.69-0.90). The risk of major bleeding was higher with dabigatran 150mg twice daily and rivaroxaban 20mg twice daily vs. apixaban 5mg twice daily, and with rivaroxaban 20mg twice daily vs. edoxaban 60mg once daily. 

Intracranial bleeding risk was substantially lower for most DOACs vs. warfarin but the risk of gastrointestinal bleeding was greater with some DOACs vs. warfarin. 

“Apixaban 5mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin,” the authors stated. As some DOACs demonstrated benefit over warfarin, the authors call for a study to directly compare DOACs. 

For more information visit bmj.com.