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Rivaroxaban monotherapy noninferior to combo therapy for AF, stable CAD
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PARIS — In the AFIRE trial, rivaroxaban monotherapy was noninferior to rivaroxaban plus an antiplatelet agent with respect to CV events and death from any cause, and was superior for major bleeding in patients with atrial fibrillation and stable CAD.
Among 2,236 patients randomly assigned rivaroxaban only or rivaroxaban plus a single antiplatelet agent, monotherapy was noninferior to combination therapy for the primary efficacy endpoint — a composite of stroke, systemic embolism, MI, unstable angina requiring revascularization or death from any cause. The event rate at 24 months of follow-up was 4.14% per patient-year vs. 5.75% per patient-year (HR = 0.72; 95% CI, 0.55-0.95; P for noninferiority < .001), Satoshi Yasuda, MD, PhD, from the department of cardiovascular medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan, reported during a Hot Line Session at the European Society of Cardiology Congress.
For the primary safety endpoint — International Society on Thrombosis and Hemostasis major bleeding — rivaroxaban monotherapy was superior to the combination therapy. The event rates were 1.62% per patient-year vs. 2.76% per patient-year (HR = 0.59; 95% CI, 0.39-0.89; P for superiority = .01).
Of note, the rivaroxaban dose used in this study was the dose approved in Japan: 10 mg or 15 mg once daily, according to the patient’s creatinine clearance. This is an important limitation of the trial, Yasuda said here.
The data were published simultaneously in The New England Journal of Medicine.
The open-label trial enrolled patients with AF who underwent PCI or CABG more than a year earlier or who had angiographically confirmed CAD that did not require revascularization. The median CHADS-VASc score was 2 and median CHADS-VASc score was 4. Patients were randomly assigned to rivaroxaban 10 mg or 15 mg per day or rivaroxaban plus a single antiplatelet agent, including aspirin (81 mg or 100 mg/day), clopidogrel (50 or 75 mg/day) or prasugrel (3.5 mg or 3.75 mg/day). Aspirin was the primary antiplatelet agent used in AFIRE.
The AFIRE trial was stopped early because of a higher risk for death from any cause in the combination therapy group. At the time of termination, median treatment duration was 23 months and median follow-up period was 24.1 months, according to the simultaneous publication.
“At 2 years, monotherapy was noninferior to combination therapy with respect to ischemic events and superior with respect to major bleeding,” Yasuda said. “Our results support the general concept that rivaroxaban monotherapy without antiplatelet therapy is the better approach for patients with AF and stable CAD.”
Yasuda cited several limitations of the study, including its open-label design and early termination, which may overestimate the efficacy data.
During a discussion of the trial, Freek W.A. Verheugt, MD, from the Heart-Lung Center of the University Center of Nijmegen and the department of cardiology at Onze Lieve Vrouwe Gasthuis, the Netherlands, put these findings in context.
“The AFIRE results confirm the EU and U.S. guidelines to quit antiplatelet therapy 1 year after PCI in AF patients on oral anticoagulation: stopping at 1 year is safer and more effective than continuation and, most of all, it saves lives. Yet, since an earlier and smaller Japanese study [OAC-ALONE] did not show a benefit of stopping antiplatelet therapy at 1 year, the AFIRE results should be confirmed in a next large trial, preferably in a non-Asian population.”
Richard Becker, MD, from the department of medicine at University of Cincinnati College of Medicine and an American Heart Association volunteer expert, provided his insights on antithrombotic therapy in AF and stable CAD in an editorial published in NEJM.
“Do the collective data from the AFIRE and OAC-ALONE trials provide definitive guidance for clinicians who are treating patients in this population? In my judgement, they do add an element of support for current guidelines and underscore the potential effect of direct oral anticoagulants on the pathobiology of coronary artery disease and cardioembolic events in patients with atrial fibrillation, but they fall short of securing level 1 and class A evidence. Further investigation will be required,” Becker wrote. – by Katie Kalvaitis and Erik Swain
References:
Yasuda S. Hot Line Session 3. Presented at: European Society of Cardiology Congress; Aug. 31-Sept. 4, 2019; Paris.
Becker RC. N Engl J Med. 2019;doi:10.1056/NEJMe1910560.
Yasuda S, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1904143.
Disclosures: Yasuda reports he receives research contracts from Takeda, financial ties with Abbott, and consulting/royalties/owner/stockholder for Bristol-Myers Squibb and Daiichi Sankyo. Becker reports he receives personal fees from Akcea, Janssen, Mercator and Portola. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Angelo Biviano, MD, MPH
One of the biggest challenges of managing this patient population is balancing the bleeding risk from being on anticoagulants and antithrombotics, particularly severe gastrointestinal bleeding or intracranial bleeding, with the thrombotic risk. The cardiology community has been grappling with this issue for years, including now as the newer anticoagulants have been introduced. Fine-tuning our treatment regimen for these patients is a major challenge.
The AFIRE study is helping us to fill in the gap in the knowledge base on the optimal medical regimen for patients who have AF and stable coronary disease. Guidelines have been evolving to reflect that most patients seem to do well with a step-down approach to treatment, particularly those patients who have more recent active coronary disease. But we have not had many trials able to guide us on what to do with more stable coronary disease, which made up the population in this trial.
If bleeding risk and death can be decreased while there is noninferiority for major CV events without having to use an extra agent such as aspirin, that’s a powerful statement that we have to look into further.
There are some limitations to this study which will perhaps temper widespread use of rivaroxaban monotherapy. These include that these patients are from Japan and there are differences with regard to metabolism of medications in that population, so generalizability to a U.S. population is not proven; the dose of rivaroxaban was different from that which is given in the U.S. to patients with AF; and most of the patients were men. The study is a steppingstone and a guide, but we are not there yet in terms of putting this approach front and center in the guidelines.
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