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Safety and Effectiveness of Rivaroxaban in Combination with Various Antiarrhythmic Drugs in Patients with Non-Permanent Atrial Fibrillation

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Abstract

Introduction

Rivaroxaban reduces the risk of thromboembolism in atrial fibrillation (AF) patients, who often also receive antiarrhythmic drugs (AADs) to maintain sinus rhythm. Current guidelines contraindicate concomitant use of rivaroxaban with the popular AAD dronedarone, despite little data demonstrating interactions with AADs. This study investigates the outcomes of concomitant rivaroxaban and AAD drug use in a real-world cohort.

Methods

This retrospective study included 1777 non-permanent AF patients taking rivaroxaban for ≥ 1 month between 2011 and 2016 from a multicenter cohort in Taiwan, and compared concomitant AAD use against clinical outcome endpoints for safety, effectiveness, and major adverse cardiac events (MACE). Multivariate Cox proportional hazard analyses were used to evaluate the association between concomitant AAD use and outcomes.

Results

Patients were divided into rivaroxaban alone (n = 1205) and with concomitant amiodarone (n = 177), dronedarone (n = 231), or propafenone (n = 164) groups. The proportion of patients using rivaroxaban 10 mg was highest in the concomitant dronedarone group: rivaroxaban alone, 53.6%; with amiodarone, 57.6%; with dronedarone, 77.1%; and with propafenone, 46.3% (p < 0.001). The cumulative incidences of safety (p = 0.892), effectiveness (p = 0.336), and MACE (p = 0.674) were similar between the four groups; however, there were significantly fewer new systemic thromboembolisms in the dronedarone group: rivaroxaban alone, 2.5%; with amiodarone, 0.6%; with dronedarone, 0%; and with propafenone, 1.2% (p = 0.029). The all-cause death rate was also lowest in the dronedarone group: rivaroxaban alone, 9.0%; with amiodarone, 9.6%; with dronedarone, 3.0%; and with propafenone: 6.1% (p = 0.013). After covariate adjustment, there were no differences in the safety, effectiveness, and MACE endpoints between patients receiving or not receiving AADs.

Conclusion

Concomitant use of rivaroxaban with AADs appears to be well tolerated, warranting further investigation into the apparent benefits of a reduced dose of rivaroxaban combined with dronedarone.

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Authors and Affiliations

  1. Division of Cardiology, Taitung MacKay Memorial Hospital, Taitung, Taiwan

    Wei-Ru Chiou & Min-I Su

  2. Department of Medicine, Mackay Medical College, New Taipei, Taiwan

    Wei-Ru Chiou, Lawrence Yu-Min Liu, Jen-Yuan Kuo, Yih-Jer Wu & Ying-Hsiang Lee

  3. Department of Healthcare Administration, I-Shou University, Kaohsiung, Taiwan

    Chun-Che Huang

  4. Division of Cardiology, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan

    Po-Lin Lin & Lawrence Yu-Min Liu

  5. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

    Po-Lin Lin

  6. Department of Medical Education, MacKay Memorial Hospital, Taipei, Taiwan

    Jen-Yu Chuang

  7. Cardiovascular Center, MacKay Memorial Hospital, 92, Zhongshan North Road Section 2, Zhongshan District, Taipei, Taiwan

    Feng-Ching Liao, Chun-Yen Chen, Jen-Yuan Kuo, Cheng-Ting Tsai, Yih-Jer Wu & Ying-Hsiang Lee

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  1. Wei-Ru Chiou
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Corresponding author

Correspondence to Ying-Hsiang Lee.

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Funding

No external funding was used in the preparation of this manuscript.

Conflicts of interest/Competing interests

Wei-Ru Chiou, Chun-Che Huang, Po-Lin Lin, Jen-Yu Chuang, Lawrence Yu-Min Liu, Min-I Su, Feng-Ching Liao, Chun-Yen Chen, Jen-Yuan Kuo, Cheng-Ting Tsai, Yih-Jer Wu, and Ying-Hsiang Lee declare they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval

The Institutional Review Board of MacKay Memorial Hospital approved the study protocol (IRB No. 16MMHIS009), which waived the requirement for informed consent in this retrospective study.

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Not applicable.

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Not applicable.

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Not applicable.

Code availability

Not applicable.

Author contributions

W-RC: Conceptualization, primary author, review and editing, data collection, data interpretation, data resources. C-CH: Data analysis, data interpretation, writing – review and editing. P-LL: Conceptualization, data collection, data resources. J-YC: Writing – original draft. Lawrence Y-ML: Data collection, data resources. M-IS: Conceptualization, data resources. F-CL: Data collection, data resources. C-YC: Data resources. J-YK: Data resources. C-TT: Data resources. Y-JW: Supervision, data resources. Y-HL: Conceptualization, project administration, writing – review and editing, methodology, data collection, data resources.

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Chiou, WR., Huang, CC., Lin, PL. et al. Safety and Effectiveness of Rivaroxaban in Combination with Various Antiarrhythmic Drugs in Patients with Non-Permanent Atrial Fibrillation. Am J Cardiovasc Drugs 21, 459–469 (2021). https://doi.org/10.1007/s40256-020-00454-6

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