Connie N Hess1, Stefan James2, Renato D Lopes1, Daniel M Wojdyla1, Megan L Neely1, Danny Liaw3, Emil Hagstrom1, Deepak L Bhatt4, Steen Husted5, Shaun G Goodman6, Basil S Lewis7, Freek W A Verheugt8, Raffaele De Caterina9, Hisao Ogawa10, Lars Wallentin2, John H Alexander11. 1. Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina. 2. Uppsala Clinical Research Institute, Uppsala University, Uppsala, Sweden. 3. Bristol-Myers Squibb, Princeton, New Jersey. 4. Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. 5. Århus University Hospital, Århus, Denmark. 6. Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 7. Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel. 8. University Medical Center of Nijmegen, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands. 9. Institute of Cardiology, G. d'Annunzio University-Chieti, Chieti, Italy. 10. Division of Cardiology, Kumamoto University, School of Medicine, Kumamoto City, Japan. 11. Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina. Electronic address: john.h.alexander@dm.duke.edu.
Abstract
BACKGROUND: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES: 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 withaspirin 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 onaspirin 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).
RCT Entities:
BACKGROUND: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES: 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).
Authors: Florentino Lupercio; Shaun Giancaterino; Pedro Arturo Villablanca; Frederick Han; Kurt Hoffmayer; Gordon Ho; Farshad Raissi; David Krummen; Ulrika Birgersdotter-Green; Gregory Feld; Ryan Reeves; Ehtisham Mahmud; Jonathan C Hsu Journal: Heart Date: 2020-02-07 Impact factor: 5.994
Authors: Samer Al Said; Samer Alabed; Klaus Kaier; Audrey R Tan; Christoph Bode; Joerg J Meerpohl; Daniel Duerschmied Journal: Cochrane Database Syst Rev Date: 2019-12-19
Authors: Wolf-Stephan Rudi; Michael Molitor; Venkata Garlapati; Stefanie Finger; Johannes Wild; Thomas Münzel; Susanne H Karbach; Philip Wenzel Journal: Antioxidants (Basel) Date: 2021-03-05