AFIRE trial gives two good reasons against combination with antiplatelet
PARIS -- Adding an antiplatelet to rivaroxaban (Xarelto) for atrial fibrillation in stable coronary artery disease may backfire, the Japanese AFIRE trial affirmed.
The trial had to be stopped early for mortality risk with the combination compared with rivaroxaban alone (3.37% vs 1.85% per patient-year, HR 0.55 for monotherapy, 95% CI 0.38-0.81), which was significantly higher for both cardiovascular and noncardiovascular causes.
While the antiplatelet-anticoagulant combination came out noninferior for the composite primary efficacy endpoint of stroke, systemic embolism, MI, unstable angina requiring revascularization, or death from any cause (5.75% vs 4.14%, HR 0.72 for monotherapy, 95% CI 0.55-0.95), monotherapy was actually significantly superior in a post hoc assessment.
Monotherapy also led to less TIMI major bleeding (1.62% vs 2.76% per patient-year, HR 0.59, 95% CI 0.39-0.89, P=0.01 for superiority), Satoshi Yasuda, MD, PhD, of the Japan Cardiovascular Research Foundation in Osaka, and colleagues reported here at the European Society of Cardiology meeting and online in The New England Journal of Medicine.
The findings support both U.S. and European guidelines that suggest monotherapy after 12 months of combination therapy and for those not requiring intervention, but which were based on only weak evidence, said ESC session discussant Freek Verheugt, MD, PhD, of the Heartcenter of the University Medical Center of Nijmegen, The Netherlands.
Session moderator Frank Ruschitzka, MD, of the University of Zurich, suggested that the trial may move from IIa to Ib in guidelines.
However, the data "fall short of securing level 1 and class A evidence," concluded Richard Becker, MD, of the University of Cincinnati, in an accompanying editorial.
The open-label trial included 2,236 patients with atrial fibrillation who had coronary revascularization (largely percutaneous coronary intervention, 70%) more than one year earlier or who had angiographically-confirmed coronary artery disease without revascularization.
Randomized treatment with rivaroxaban monotherapy or the combination with aspirin or a P2Y12 receptor antagonist at the physicians' discretion (clopidogrel [Plavix] for about 25%) continued for a median 23 months before discontinuation of the trial.
Japan's approved dose of 10 or 15 mg, depending on renal function, has been shown to yield a blood level in Japanese patients comparable to that among white patients taking the 20 mg typical in Western countries, Yasuda noted.
"The way we treat patients and the characteristics of patients with atrial fibrillation are similar throughout the world, so I think this will be quite generalizable to other countries," Alessia Gimelli, MD, of the CNR Institute of Clinical Physiology in Pisa, Italy, said as an ESC spokesperson at a press conference for the late-breaking clinical trial session.
However, Ruschitzka suggested that generalizability to other populations and different dosing strategies and different non-vitamin K oral anticoagulants is an open question until studied.
Verheugt noted that the AQUATIC randomized trial from France should provide confirmation outside an Asian population.
Two fatal bleeds occurred in each group.
Findings were consistent for both efficacy and safety across subgroups, including sex, age, stroke and bleeding risk scores, stent type, and renal function. No interaction was seen between the primary endpoint and use of aspirin versus P2Y12 inhibitors, but this needs to be further examined, Yasuda said.
His group acknowledged that "the reductions in the rate of ischemic events and death from any cause with rivaroxaban monotherapy were unanticipated and are difficult to explain on the basis of the biologic effects of antithrombotic therapy; these findings may be due to the play of chance."
The trial was supported by the Japan Cardiovascular Research Foundation through a contract with Bayer Yakuhin.
Yasuda disclosed relationships with Takeda, Daiichi-Sankyo, Bristol-Myers Squibb, and Abbott.
New England Journal of Medicine
Source Reference: Yasuda S, et al "Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease" N Engl J Med 2019; DOI: 10.1056/NEJMoa1904143.
New England Journal of Medicine
Source Reference: Becker RC "Antithrombotic Therapy in Atrial Fibrillation and Coronary Artery Disease" N Engl J Med 2019; DOI: 10.1056/NEJMe1910560.
Read the original article on Medpage Today: NOAC Best Given Alone for Afib With Stable Heart Disease