Comparative efficacy and safety of new oral anticoagulants in patients with atrial fibrillation.
BACKGROUND
Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.


RESULTS
We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban.


CONCLUSIONS
An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
Department of Medicine, Harvard Medical School, Boston, MA, USA. schneeweiss@post.harvard.edu
Sebastian
S
Schneeweiss
Joshua J
JJ
Gagne
Amanda R
AR
Patrick
Niteesh K
NK
Choudhry
Jerry
J
Avorn
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran; D004617:Embolism / Q000209:etiology / Q000517:prevention & control*; D019317:Evidence-Based Medicine; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000925:Anticoagulants; D001562:Benzimidazoles; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran