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Original Research: Cardiovascular Disease |

Risk of Serious Atrial Fibrillation and Stroke With Use of BisphosphonatesAtrial Fibrillation, Stroke, and Bisphosphonate: Evidence From a Meta-analysis

Abhishek Sharma, MD; Saurav Chatterjee, MD; Armin Arbab-Zadeh, MD, PhD; Sandeep Goyal, MD; Edgar Lichstein, MD; Joydeep Ghosh, MD; Shamik Aikat, MD
Author and Funding Information

From the Department of Medicine (Drs Sharma and Lichstein), Maimonides Medical Center, Brooklyn, NY; the Division of Cardiology (Dr Ghosh), New York-Presbyterian/Columbia University Medical Center, New York, NY; the Division of Cardiology (Dr Chatterjee), Providence VA Medical Center, and Brown University (Dr Chatterjee), Providence, RI; the Division of Cardiology (Dr Arbab-Zadeh), Johns Hopkins University School of Medicine, Baltimore, MD; the Division of Cardiology (Dr Goyal), Vanderbilt University Medical Center, Nashville, TN; and the Division of Cardiology (Dr Aikat), Lexington VA Hospital, Lexington, KY.

Correspondence to: Abhishek Sharma, MD, 1016 50th St, Apt 2C, Brooklyn, NY 11219; e-mail: abhisheksharma4mamc@gmail.com


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(4):1311-1322. doi:10.1378/chest.13-0675
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Background:  Clinical studies have suggested an association between bisphosphonate use and the onset of atrial fibrillation (AF). However, data on the risk of developing AF, stroke, and cardiovascular mortality with the use of bisphosphonate are conflicting. The objective of this study was to evaluate the risk of serious AF (events that required hospital admission), stroke, and cardiovascular mortality with the use of bisphosphonates through a systematic review of the literature.

Methods:  We searched the PubMed, CENTRAL, and EMBASE databases for observational studies and randomized controlled trials (RCTs) on the use of bisphosphonates from 1966 to April 2012 that reported the number of patients who developed serious AF, stroke, and cardiovascular mortality at follow-up. The random-effects Mantel-Haenszel test was used to evaluate relative risk-adverse cardiovascular outcomes with the use of bisphosphonates.

Results:  Six observational studies (n = 149,856) and six RCTs (n = 41,375) were included for analysis. On pooling observational studies, there was an increased risk of AF (OR, 1.27; 95% CI, 1.16-1.39) among bisphosphonate users. Further, analysis of RCTs revealed a statistically significant increase in the risk of serious AF (OR, 1.40; 95% CI, 1.02-1.93) and no increase in the risk of stroke (OR, 1.07; 95% CI, 0.85-1.34) or cardiovascular mortality (OR, 0.92; 95% CI, 0.68-1.26) with the use of bisphosphonates.

Conclusions:  Evidence from RCTs and observational studies suggests a significantly increased risk of AF requiring hospitalization, but no increase in risk of stroke or cardiovascular mortality, with the use of bisphosphonate.

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