TY - JOUR
T1 - Apixaban with antiplatelet therapy after acute coronary syndrome
AU - Alexander, John H.
AU - Lopes, Renato D.
AU - James, Stefan
AU - Kilaru, Rakhi
AU - He, Yaohua
AU - Mohan, Puneet
AU - Bhatt, Deepak L.
AU - Goodman, Shaun
AU - Verheugt, Freek W.
AU - Flather, Marcus
AU - Huber, Kurt
AU - Liaw, Danny
AU - Husted, Steen E.
AU - Lopez-Sendon, Jose
AU - De Caterina, Raffaele
AU - Jansky, Petr
AU - Darius, Harald
AU - Vinereanu, Dragos
AU - Cornel, Jan H.
AU - Cools, Frank
AU - Atar, Dan
AU - Leiva-Pons, Jose Luis
AU - Keltai, Matyas
AU - Ogawa, Hisao
AU - Pais, Prem
AU - Parkhomenko, Alexander
AU - Ruzyllo, Witold
AU - Diaz, Rafael
AU - White, Harvey
AU - Ruda, Mikhail
AU - Geraldes, Margarida
AU - Lawrence, Jack
AU - Harrington, Robert A.
AU - Wallentin, Lars
PY - 2011/8/25
Y1 - 2011/8/25
N2 - 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.)
AB - 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.)
UR - https://www.scopus.com/pages/publications/80052162121
U2 - 10.1056/NEJMoa1105819
DO - 10.1056/NEJMoa1105819
M3 - Article
C2 - 21780946
AN - SCOPUS:80052162121
SN - 0028-4793
VL - 365
SP - 699
EP - 708
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 8
ER -