Comparison of efficacy and safety of dabigatran, rivaroxaban and apixaban in patients with atrial fibrillation using network meta-analysis.
OBJECTIVE
A network meta-analysis of the three new oral anticoagulants was performed from the three trials comparing dabigatran, rivaroxaban and apixaban with warfarin in patients with atrial fibrillation.


METHODS
Data were extracted of the RE-LY study of dabigatran 110 mg bid and dabigatran 150 mg bid, the ROCKET AF trial of rivaroxaban and the ARISTOTLE trial of apixaban for the composite outcome of ischemic stroke and systemic embolism, for major bleeding, intracerebral bleeding, mortality and myocardial infarction.


RESULTS
Dabigatran (150 mg bid) showed superior efficacy in preventing ischemic stroke plus systemic embolism to dabigatran (110 mg bid, P=0.0364) and rivaroxaban (P=0.0388). Apixaban had equivalent efficacy with rivaroxaban and dabigatran (either dose). Apixaban was safer (less major bleeding) than dabigatran (150 mg bid, P=0.036) or rivaroxaban (P=0.0002). Intracerebral hemorrhage occurred with equal frequency for all agents except for rivaroxaban (higher risk than dabigatran 110 mg bid, P=0.0070). Myocardial infarction occurred less frequently with rivaroxaban and apixaban compared to either dose of dabigatran (all P<0.05).


CONCLUSIONS
All-cause mortality was not different for any agent or regimen. In the absence of head-to-head comparisons, this network meta-analysis suggests that apixaban and dabigatran 110 mg bid may offer the best benefit-risk balance for stroke prevention in non-valvular atrial fibrillation. Dabigatran 150 mg bid may be preferred for patients with a high risk for embolism.
Department of Clinical Pharmacology Faculty of Medicine Mannheim, Ruprecht-Karls-University Heidelberg, Germany. job.harenberg@medma.uni-heidelberg.de
J
J
Harenberg
S
S
Marx
H-C
HC
Diener
G Y H
GY
Lip
V J
VJ
Marder
M
M
Wehling
C
C
Weiss
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D016009:Chi-Square Distribution; D000069604:Dabigatran; D004617:Embolism / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000209:etiology; D016017:Odds Ratio; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D015091:beta-Alanine / Q000008:administration & dosage / 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; D000069552:Rivaroxaban; D000069604:Dabigatran