Author + information
- Received July 30, 2019
- Revision received October 28, 2019
- Accepted October 29, 2019
- Published online January 20, 2020.
- Toshiki Kuno, MD, PhDa,∗ (, )@ToshikiKuno,
- Hisato Takagi, MD, PhDb,
- Tomo Ando, MDc,
- Takehiro Sugiyama, MD, MSHS, PhDd,e,f,
- Satoshi Miyashita, MDa,
- Nelson Valentin, MD, MSca,
- Yuichi J. Shimada, MD, MPHg,
- Masaki Kodaira, MD, PhDh,
- Yohei Numasawa, MD, PhDh,
- Alexandros Briasoulis, MD, PhDi,
- Alfred Burger, MDa and
- Sripal Bangalore, MD, MHAj
- aDepartment of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, New York
- bDepartment of Cardiovascular Surgery, Shizuoka Medical Center, Shizuoka, Japan
- cDepartment of Cardiology, Detroit Medical Center, Detroit, Michigan
- dDiabetes and Metabolism Information Center, Research Institute, Center for Global Health and Medicine, Tokyo, Japan
- eDepartment of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
- fDepartment of Public Health/Health Policy, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan
- gDivision of Cardiology, Department of Medicine, Columbia University Medical Center, New York, New York
- hDepartment of Cardiology, Japanese Red Cross Ashikaga Hospital, Ashikaga, Japan
- iDivision of Cardiovascular Medicine, Section of Heart Failure and Transplantation, University of Iowa, Iowa City, Iowa
- jDivision of Cardiovascular Medicine, New York University School of Medicine, New York, New York
- ↵∗Address for correspondence:
Dr. Toshiki Kuno, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, First Avenue, 16th Street, New York, New York 10003.
Background Patients on long-term dialysis are at increased risk of bleeding. Although oral anticoagulants (OACs) are recommended for atrial fibrillation (AF) to reduce the risk of stroke, randomized trials have excluded these populations. As such, the net clinical benefit of OACs among patients on dialysis is unknown.
Objectives This study aimed to investigate the efficacy and safety of OACs in patients with AF on long-term dialysis.
Methods MEDLINE and EMBASE were searched through June 10, 2019, for studies that investigated the efficacy and safety of different OAC strategies in patients with AF on long-term dialysis. The efficacy outcomes were ischemic stroke and/or systemic thromboembolism, all-cause mortality, and the safety outcome was major bleeding.
Results This study identified 16 eligible observational studies (N = 71,877) regarding patients on long-term dialysis who had AF. Only 2 of 16 studies investigated direct OACs. Outcomes for dabigatran and rivaroxaban were limited to major bleeding events. Compared with no anticoagulants, apixaban and warfarin were not associated with a significant decrease in stroke and/or systemic thromboembolism (apixaban 5 mg, hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.30 to 1.17; apixaban 2.5 mg, HR: 1.00; 95% CI: 0.52 to 1.93; warfarin, HR: 0.91; 95% CI: 0.72 to 1.16). Apixaban 5 mg was associated with a significantly lower risk of mortality (vs. warfarin, HR: 0.65; 95% CI: 0.45 to 0.93; vs. apixaban 2.5 mg, HR: 0.62; 95% CI: 0.42 to 0.90; vs. no anticoagulant, HR: 0.61; 95% CI: 0.41 to 0.90). Warfarin was associated with a significantly higher risk of major bleeding than apixaban 5 min/2.5 mg and no anticoagulant (vs. apixaban 5 mg, HR: 1.41; 95% CI: 1.07 to 1.88; vs. apixaban 2.5 mg, HR: 1.40; 95% CI: 1.07 to 1.82; vs. no anticoagulant, HR: 1.31; 95% CI: 1.15 to 1.50). Dabigatran and rivaroxaban were also associated with significantly higher risk of major bleeding than apixaban and no anticoagulant.
Conclusions This meta-analysis showed that OACs were not associated with a reduced risk of thromboembolism in patients with AF on long-term dialysis. Warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk compared with apixaban and no anticoagulant. The benefit-to-risk ratio of OACs in patients with AF on long-term dialysis warrants validation in randomized clinical trials.
Dr. Shimada is supported in part by unrestricted grants from the American Heart Association National Clinical and Population Research Award and Career Development Award, Honjo International Scholarship Foundation, and Korea Institute of Oriental Medicine. Dr. Bangalore is supported by grants from Abbott Vascular and the National Heart, Lung, and Blood Institute; and is a member of the Advisory Board of Abbott Vascular, Biotronik, Amgen, Pfizer, and Reata. Dr. Burger holds stock in Potola Pharmaceutical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Louise Pilote, MD, MPH, PhD, served as Guest Associate Editor for this paper.
- Received July 30, 2019.
- Revision received October 28, 2019.
- Accepted October 29, 2019.
- 2020 American College of Cardiology Foundation
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