JCS/JHRS Guideline: Rivaroxaban Not Recommended for Patients With Nonvalvular Atrial Fibrillation and High Bleeding Risk

To the Editor:

We find it surprising that rivaroxaban has been omitted from the recommended direct oral anticoagulants (DOACs) for prevention of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) and high bleeding risk (HBR) in the JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias.¹ The reason for this omission may be that rivaroxaban did not demonstrate a significant reduction in major bleeding compared with warfarin in J-Rocket AF.

However, indirect comparisons between phase 3 studies should be interpreted with care because of recognized differences in patient characteristics and methodology (e.g., target INR for warfarin).

In all phase 3 studies of DOACs, patients with a history of bleeding were excluded as HBR. Some studies excluded patients requiring dual-antiplatelet therapy or chronic non-aspirin NSAIDs. Consequently, patients at HBR were not evaluated in these studies.

Furthermore, in the subgroup analyses of Asian patients cited in the guideline, all P-values in RE-LY were nominal because of the low number of Asian patients.² Additionally, in ENGAGE AF-TIMI 48, the lower number of East-Asian vs. non-Asian patients did not provide sufficient power for statistical comparisons between the outcomes of the 2 groups.³

In conclusion, we believe that the omission of rivaroxaban from the JCS/JHRS 2020 Guideline recommendations for patients with NVAF and HBR was inappropriate.

Acknowledgments

We thank Dr. Jim Purvis of Oxford PharmaGenesis for writing assistance.

Disclosures

A. Hirayama received lecture fees from Daiichi-Sankyo Co., Bayer Yakuhin Ltd., Takeda Pharma. Co. Ltd., and Astra-Zeneca K.K. and is a member of Circulation Journal’s Editorial Team. T. Hayasaki and M. Tachiiri are employees of Bayer Yakuhin.

• Atsushi Hirayama, MD
• Department of Cardiology, Osaka Police Hospital, Osaka, Japan
• Norio Tanahashi, MD
• Department of Neurology, Saitama Medical University International Medical Center, Saitama, Japan
• Michiya Tachiiri, MD
• Takanori Hayasaki, MD
• Medical Affairs, Bayer Yakuhin, Ltd., Osaka, Japan

References

• 1.   Ono K, Iwasaki Y, Akao M, Ikeda T, Ishii K, Inden Y, et al. JCS/JHRS 2020 guideline on pharmacotherapy of cardiac arrhythmias. Circ J, doi:10.1253/circj.CJ-20-1212.
• 2.   Hori M, Connolly SJ, Zhu J, Liu LS, Lau CP, Pais P, et al. Dabigatran versus warfarin: Effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013; 44: 1891–1896.
• 3.   Yamashita T, Koretsune Y, Yang Y, Chen SA, Chung N, Shimada YJ, et al. Edoxaban vs warfarin in East Asian patients with atrial fibrillation: An ENGAGE AF-TIMI 48 subanalysis. Circ J 2016; 80: 860–869.