Net stroke equivalents for antithrombotic therapy prescribed for atrial fibrillation

Purpose: To conduct a systematic review of antithrombotic therapy for atrial fibrillation.

Methods: Data sources that were searched included Pubmed, EMBASE, MEDLINE, and Clinicaltrials.gov.  We conducted a systematic analysis of phase 3 clinical trials using the keywords apixaban, dabigatran, rivaroxaban, and atrial fibrillation [MeSH] by two independent reviewers.  Of 196 studies, the primary studies of RE-LY, ROCKET-AF, ARISTOTLE, AVERROES, ACTIVE-A, and ACTIVE-W were selected for our analysis.  The antithrombotics used in these studies were evaluated by adjusting for the time in therapeutic range (TTR) for International Normalized Ratio (INR).  The rates of stroke, intracranial hemorrhage, extracranial hemorrhage, and myocardial infarction were calculated from the relative risk of each event compared to warfarin.  These adverse events were converted into stroke equivalents based on quality adjusted life years lost.

Results: The optimal antithrombotic therapy depended on risk of stroke, as estimated by CHADS₂ score.  For patients with a CHADS₂ score of 1, either apixaban or dabigatran had the lowest rates of stroke and stroke equivalents, while aspirin (with or without clopidogrel) had the highest rates.  For CHADS₂ scores of 2 or more, dabigatran 150 mg bid had the lowest rates of stroke and stroke equivalents, but this treatment had the highest rates of myocardial infarction and relatively high rates of gastrointestinal hemorrhage.  There was insufficient information to quantify the effect of the new anticoagulants in patients with a CHADS₂ score of 0.  Although rivaroxaban had the advantage of once daily dosing, it was not the optimal therapy for any CHADS₂ score.

Conclusion: We recommend dabigatran or apixaban twice daily for stroke prophylaxis in patients with atrial fibrillation who have a CHADS₂ score of 1 and dabigatran 150 mg twice daily for patients with a higher CHADS₂ score.