DOAC monotherapy reduces total adverse events in AF and stable coronary artery disease
Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial
Introduction and methods
As primary efficacy and safety assessments in many clinical trials rely on time-to-first-event analyses, these studies fail to capture the true disease burden. In the recent AFIRE trial, rivaroxaban monotherapy was associated with a lower risk of first cardiovascular and major bleeding events in patients with AF and stable coronary artery disease (CAD) when compared to standard combination therapy . To assess the incidence of all events in this trial, a post-hoc secondary analysis was undertaken.
Aim of the study
The aim of this secondary analysis was to compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and rivaroxaban and antiplatelet combination therapy in patients with AF and stable CAD.
The AFIRE trial was a multicenter, prospective, open-label study conducted in Japan in which patients with nonvalvular AF, stable CAD, and CHADS2 score ≥1 were randomized to monotherapy with rivaroxaban (10 or 15 mg once daily, based on patient’s creatinine clearance) or combination therapy with rivaroxaban and an antiplatelet agent (aspirin or P2Y12 inhibitor, at the treating physician’s discretion). Only patients who had undergone PCIor CABG ≥1 year earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. In the secondary analysis, a modified intention-to-treat analysis, 2215 patients were included.
The primary end point was the total number of first and subsequent events, including death from any cause, bleeding events, and thrombotic events. Bleeding events were a composite outcome of hemorrhagic stroke or major bleeding, defined according to the International Society on Thrombosis and Hemostasis criteria. Thrombotic events were a composite outcome of ischemic stroke, systemic embolism, MI, or unstable angina requiring revascularization.
- During a median follow-up duration of 24.1 months (IQR: 17.3–31.5), the number of total events was 135 in the rivaroxaban monotherapy group (n=1107; total event rate: 12.2%) and 213 in the combination-therapy group (n=1108; total event rate: 19.2%).
- Rivaroxaban monotherapy was associated with a 38% lower risk of total events compared with combination therapy (hazard ratio: 0.62; 95%CI: 0.48–0.80; P<0.001).
- Monotherapy resulted in a 31% lower rate of first events compared with combination therapy (rate ratio: 0.69; 95%CI: 0.55–0.87) and a 54% lower incidence of subsequent events (rate ratio: 0.46; 95%CI: 0.29–0.74).
- The mortality rate was 3.7% (41/1107) in the monotherapy group and 6.6% (73/1108) in the combination-therapy group.
- Death accounted for 28.3% (77/272) of the first events and for 48.7% (37/76) of the subsequent events.
- Bleeding events occurred more frequently than thrombotic events regardless of the type of first event.
- Among the patients who had a first thrombotic or bleeding event and subsequently died, bleeding events accounted for 75% (6/8) in the monotherapy group and for 62.1% (18/29) in the combination-therapy group, indicating that bleeding events were clinically more impactful than thrombotic events.
Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events—both first and subsequent events—in patients with AF and stable CAD compared with rivaroxaban and antiplatelet combination therapy. According to the authors, tapering antithrombotic therapy should be considered in AF patients after PCI to minimize bleeding events. They also believe that “[e]valuating the total number of events may provide a more comprehensive estimate of the treatment benefit when the study medication has been shown to reduce the first occurrence of the end point.”