Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Insights From the APPRAISE-2 Trial.
BACKGROUND
Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS).


OBJECTIVE
We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS.


METHODS
This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate.


RESULTS
At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p(interaction)= 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p(interaction)= 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention.


CONCLUSIONS
Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2]; NCT00831441).
Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
Connie N
CN
Hess
Uppsala Clinical Research Institute, Uppsala University, Uppsala, Sweden.
Stefan
S
James
Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
Renato D
RD
Lopes
Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
Daniel M
DM
Wojdyla
Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
Megan L
ML
Neely
Bristol-Myers Squibb, Princeton, New Jersey.
Danny
D
Liaw
Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina.
Emil
E
Hagstrom
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts.
Deepak L
DL
Bhatt
Århus University Hospital, Århus, Denmark.
Steen
S
Husted
Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Shaun G
SG
Goodman
Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel.
Basil S
BS
Lewis
University Medical Center of Nijmegen, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
Freek W A
FWA
Verheugt
Institute of Cardiology, G. d'Annunzio University-Chieti, Chieti, Italy.
Raffaele
R
De Caterina
Division of Cardiology, Kumamoto University, School of Medicine, Kumamoto City, Japan.
Hisao
H
Ogawa
Uppsala Clinical Research Institute, Uppsala University, Uppsala, Sweden.
Lars
L
Wallentin
Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina. Electronic address: john.h.alexander@dm.duke.edu.
John H
JH
Alexander
D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000188:drug therapy*; D000368:Aged; D004359:Drug Therapy, Combination; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage*
D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban
acute coronary syndromes; antiplatelet therapy; antithrombotic therapy apixaban