Abstract
BACKGROUND Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a Vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a Vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the Vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a Vitamin K antagonist, aspirin, or both.
| Original language | English |
|---|---|
| Journal | New England Journal of Medicine |
| Volume | 380 |
| Issue number | 16 |
| Pages (from-to) | 1509-1524 |
| Number of pages | 16 |
| ISSN | 0028-4793 |
| DOIs | |
| Publication status | Published - 18.04.2019 |
Funding
The trial was designed and led by an academic steering committee whose members were respon- sible for the conduct of the trial. The Duke Clinical Research Institute (DCRI, Durham, NC) was the academic coordinating center. The trial was sponsored by Bristol-Myers Squibb and Pfizer. The trial protocol (available with the full text of this article at NEJM.org) and all subsequent amendments were approved by national regulatory agencies in participating countries and by institutional review boards or ethics committees at participating sites. An independent data and safety monitoring board reviewed unblinded patient-level data at regular intervals during the trial. Although Bristol-Myers Squibb assisted with data management, all the statistical analyses were performed independently at the DCRI. The initial draft of the manuscript was written by the first author and revised on the basis of comments from the other authors. All the authors vouch for the adherence of the trial to the protocol, and the first, second, and last authors vouch for the accuracy and completeness of the data and analysis. No one who is not an author contributed to writing the manuscript. The committee members and participating investigators are listed in the Supplementary Appendix, available at NEJM.org.
Research Areas and Centers
- Centers: Cardiological Center Luebeck (UHZL)
DFG Research Classification Scheme
- 2.22-12 Cardiology, Angiology
