Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome.
Alexander, John H. M.D., M.H.S.; Lopes, Renato D. M.D., Ph.D.; James, Stefan M.D., Ph.D.; Kilaru, Rakhi M.S.; He, Yaohua M.D., Ph.D.; Mohan, Puneet M.D., Ph.D.; Bhatt, Deepak L. M.D., M.P.H.; Goodman, Shaun M.D.; Verheugt, Freek W. M.D., Ph.D.; Flather, Marcus M.D.; Huber, Kurt M.D.; Liaw, Danny M.D., Ph.D.; Husted, Steen E. M.D.; Lopez-Sendon, Jose M.D.; De Caterina, Raffaele M.D.; Jansky, Petr M.D.; Darius, Harald M.D.; Vinereanu, Dragos M.D.; Cornel, Jan H. M.D.; Cools, Frank M.D.; Atar, Dan M.D.; Leiva-Pons, Jose Luis M.D.; Keltai, Matyas M.D.; Ogawa, Hisao M.D., Ph.D.; Pais, Prem M.D.; Parkhomenko, Alexander M.D.; Ruzyllo, Witold M.D.; Diaz, Rafael M.D.; White, Harvey M.D.; Ruda, Mikhail M.D.; Geraldes, Margarida Ph.D.; Lawrence, Jack M.D.; Harrington, Robert A. M.D.; Wallentin, Lars M.D., Ph.D.; the APPRAISE-2 Investigators *
[Article]
New England Journal of Medicine.
365(8):699-708, August 25, 2011.
(Format: HTML, PDF)
Background: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.
Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.
Results: The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.
Conclusions: The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.)
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