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Randomized Controlled Trial
. 2022 Aug 1;7(8):787-794.
doi: 10.1001/jamacardio.2022.1561.

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

Ryo Naito  1 , Katsumi Miyauchi  2 , Satoshi Yasuda  3   4 , Koichi Kaikita  5 , Masaharu Akao  6 , Junya Ako  7 , Tetsuya Matoba  8 , Masato Nakamura  9 , Nobuhisa Hagiwara  10 , Kazuo Kimura  11 , Atsushi Hirayama  12 , Kunihiko Matsui  13 , Hisao Ogawa  14 ; AFIRE Investigators
Collaborators, Affiliations
Randomized Controlled Trial

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

Ryo Naito et al. JAMA Cardiol. .

Abstract

Importance: Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established.

Objective: To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients.

Design, setting, and participants: This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021.

Interventions: Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy.

Main outcomes and measures: The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable.

Results: A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P < .001). Monotherapy was an independent factor associated with a lower risk of subsequent events compared with combination therapy. The mortality risk after a bleeding event (monotherapy, 75% [6 of 8]; combination therapy, 62.1% [18 of 29]) was higher than that after a thrombotic event (monotherapy, 25% [2 of 8]; combination therapy, 37.9% [11 of 29]).

Conclusions and relevance: Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events than combination therapy in patients with AF and stable CAD. Tapered antithrombotic therapy with a sole anticoagulant should be considered in these patients.

Trial registration: ClinicalTrials.gov Identifier: NCT02642419.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Miyauchi reported receiving personal fees from Amgen Astellas BioPharma, Astellas Pharma, MSD, Bayer Yakuhin, Sanofi, Takeda Pharmaceutical, Daiichi-Sankyo, Nippon Boehringer Ingelheim, and Bristol Myers Squibb. Dr Yasuda reported receiving grants from Takeda Pharmaceutical, Abbott, and Boston Scientific and personal fees from Daiichi-Sankyo and Bristol Myers Squibb. Dr Kaikita reported receiving grants from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and grants and personal fees from Bayer Yakuhin and Daiichi-Sankyo. Dr Matoba reported receiving grants from the Japan Cardiovascular Research Foundation and personal fees from Nippon Boehringer Ingelheim, Daiichi-Sankyo, AstraZeneca, and Bayer Yakuhin. Dr Akao reported receiving grants from the Japan Agency for Medical Research and Development, personal fees from Bristol Myers Squibb and Nippon Boehringer Ingelheim, and grants and personal fees from Bayer Yakuhin and Daiichi-Sankyo. Dr Ako reported receiving personal fees from Bayer Yakuhin and Sanofi and grants and personal fees from Daiichi-Sankyo. Dr Nakamura reported receiving grants and personal fees from Bayer Yakuhin, Daiichi-Sankyo, and Sanofi and personal fees from Bristol Myers Squibb and Nippon Boehringer Ingelheim. Dr Hagiwara reported receiving grants and personal fees from Bayer Yakuhin, grants from Nippon Boehringer Ingelheim, and personal fees from Bristol Myers Squibb. Dr Kimura reported receiving grants from the Japan Cardiovascular Research Foundation, grants and personal fees from Bayer Yakuhin, Daiichi-Sankyo, Sanofi, MSD, and AstraZeneca, and personal fees from Bristol Myers Squibb and Nippon Boehringer Ingelheim. Dr Hirayama reported receiving grants and personal fees from Boston Scientific Japan, Otsuka Pharmaceutical, Sanofi, Astellas Pharma, Bristol Myers Squibb, Daiichi-Sankyo, and Bayer Yakuhin, grants from Fukuda Denshi, Abbott Japan, Japan Lifeline, Takeda Pharmaceutical, and Sumitomo Dainippon Pharma, and personal fees from Toa Eiyo, Nippon Boehringer Ingelheim, Amgen Astellas BioPharma, and AstraZeneca. Dr Ogawa reported receiving personal fees from Towa Pharmaceutical, Bristol Myers Squibb, Pfizer, Toa Eiyo, Bayer Yakuhin, and Novartis Pharma. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Rate Ratios of the Monotherapy for the First and Subsequent Events Compared With Those of Combination Therapy and Mean Total Events per Treatment Group During the Trial Period
A, Rivaroxaban monotherapy compared with combination therapy yielded 31% lower event rates for the first events. B, Rivaroxaban monotherapy compared with combination therapy yielded 54% lower event rates for the subsequent events. C, The mean cumulative function was estimated using the Nelson-Aalen nonparametric method. Total events included death from any cause, hemorrhagic and ischemic stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and major bleeding, as defined according to the criteria of the International Society on Thrombosis and Hemostasis. Monotherapy yielded a significantly lower hazard of total events compared with combination therapy.
Figure 2.
Figure 2.. Distribution of First and Subsequent Events
Breakdown of the first (A) and subsequent (B) events are shown for rivaroxaban monotherapy compared with rivaroxaban plus antiplatelet therapy.
See this image and copyright information in PMC

Comment in

References

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