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Statins Reduce Bleeding Risk in Patients Taking Oral Anticoagulants for Nonvalvular Atrial Fibrillation: A Retrospective Registry Study

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Abstract

Background

The effects of statins in patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are not well-studied. This study was a historical multicenter registry of patients with NVAF taking OACs in Japan.

Methods

We excluded those patients with mechanical heart valves or a history of pulmonary or deep vein thrombosis. Overall, 7826 patients were registered on 26 February 2013 and followed until 25 February 2017. We compared those with versus without statin treatment (statin vs. no-statin groups) for the primary outcome of major bleeding and secondary outcomes of all-cause mortality, ischemic events, hemorrhagic stroke, and ischemic stroke.

Results

Statins were administered in 2599 (33%) patients. The statin group was more likely to have paroxysmal AF (37% vs. 33%; p = 0.0003), hypertension (84% vs. 76%; p < 0.0001), diabetes mellitus (41% vs. 27%; p < 0.0001), and dyslipidemia (91% vs. 30%; p < 0.0001) than the no-statin group. The cumulative incidence of major bleeding was 6.9% and 8.1% (p = 0.06). The adjusted hazard ratio [HR] (95% confidence interval [CI]) of the statin group for major bleeding was 0.77 (0.63–0.94) compared with the no-statin group. The adjusted HR (95% CI) for all-cause mortality, ischemic events, hemorrhagic stroke, and ischemic stroke were 0.58 (0.47–0.71), 0.77 (0.59–0.999), 0.85 (0.48–1.50), and 0.79 (0.60–1.05), respectively.

Conclusions

Statins significantly reduced the risk of major bleeding, all-cause mortality, and ischemic events in patients with NVAF taking OACs. Their additive benefits should be considered in routine practice and thus be further researched.

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Acknowledgments

The authors are indebted to the data managers of the Institute for Clinical Effectiveness (Ms. Makiko Ohtorii, Ms. Ai Sunagawa, Ms. Kaori Yamamoto, Ms. Sachiko Kitamura, Ms. Hirono Saito, and Ms. Saeko Nagano) for managing the data and performing the statistical analyses.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan

    Kazutaka Uchida, Fumihiro Sakakibara, Norito Kinjo, Mari Nezu, Hideki Arai & Takeshi Morimoto

  2. Department of Neurosurgery, Hyogo Medical University, Nishinomiya, Japan

    Kazutaka Uchida, Fumihiro Sakakibara & Norito Kinjo

  3. Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Okinawa, Japan

    Shinichiro Ueda

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  1. Kazutaka Uchida
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Corresponding author

Correspondence to Takeshi Morimoto.

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Funding

This study was supported in part by Bristol-Myers Squibb and JSPS KAKENHI (JP21H03176). The funders did not participate in any part of the study from conception to article preparation.

Conflicts of Interest

Kazutaka Uchida reports lecturer’s fees from Daiichi Sankyo. Shinichiro Ueda reports receiving research grants from Bristol-Myers Squibb, Chugai, Kowa, MSD, Pfizer, and Takeda; lecturer’s fee from Boehringer Ingelheim, MSD, and Taiho; and manuscript fees from Kowa. He has also served on an advisory board for Otsuka. Takeshi Morimoto reports lecturer’s fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, and Tsumura; manuscript fees from Bristol-Myers Squibb and Kowa; and advisory board fees from Novartis and Teijin. Norito Kinjo, Fumihiro Sakakibara, Mari Nezu, and Hideki Arai have no disclosures to report.

Availability of Data and Material

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

Ethics Approval

The Institutional Review Boards of all 71 participating sites approved the study protocol in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan Declaration of Helsinki.

Consent

The Institutional Review Boards approved the opt-out method in place of written informed consent.

Author Contributions

TM and SU: Study conception and design; data acquisition and management. KU, TM, FS and NK: Statistical analyses. All authors: Interpretation of the data. KU and TM: Drafting of the manuscript. FS, NK, MN, HA, and SU: Critical revision of the manuscript. All authors: Final approval of the manuscript.

Consent to participate

Written informed consent from each participant was substituted by opt-out method under the approval from the institutional review boards.

Consent for publication

Consent for publication from study participants was not obtained because the opt-out method was used.

Code availability

The code supporting the study findings are available from the corresponding author upon reasonable request.

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Uchida, K., Ueda, S., Sakakibara, F. et al. Statins Reduce Bleeding Risk in Patients Taking Oral Anticoagulants for Nonvalvular Atrial Fibrillation: A Retrospective Registry Study. Am J Cardiovasc Drugs 23, 89–99 (2023). https://doi.org/10.1007/s40256-022-00555-4

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  • DOI: https://doi.org/10.1007/s40256-022-00555-4

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