Risk of atrial fibrillation with use of oral and intravenous bisphosphonates.
Clinical studies suggest an association between bisphosphonate use and new-onset atrial fibrillation (AF). Intravenous bisphosphonates more potently increase the release of inflammatory cytokines than do oral bisphosphonates; thus, the risk of developing AF may be greater with intravenous preparations. We have evaluated incidence of new-onset AF with use of oral and intravenous bisphosphonates through a systematic review and meta-analysis of the literature. We searched PubMed, CINAHL, Cochrane Central Register of Controlled Trials, Scopus, and EMBASE databases for observational studies and randomized controlled trials (RCTs) published from 1966 to April 2013 that reported the number of patients developing AF with use of oral or intravenous bisphosphonates. The random-effects Mantel-Haenszel test was used to evaluate the relative risk of AF with use of oral and intravenous bisphosphonates. Nine studies (5 RCTs and 4 observational studies) were included in the final analysis. Pooled data from RCTs and observational studies (n = 135,347) showed a statistically significantly increased risk of new-onset AF with both intravenous (relative risk 1.40, 95% confidence interval 1.32 to 1.49) and oral (relative risk 1.22, 95% confidence interval 1.14 to 1.31) bisphosphonates. The z statistic, which assesses the difference between the 2 risk ratios, indicated higher risk of AF with intravenous bisphosphonates versus oral bisphosphonates (p = 0.03). In conclusion, pooled data from RCTs and observational studies suggest that risk of AF is increased by use of oral or intravenous bisphosphonates but further suggest that risk is relatively greater with intravenous preparations.
Department of Medicine, Maimonides Medical Center, Brooklyn, New York. Electronic address: abhisheksharma4mamc@gmail.com.
Abhishek
A
Sharma
Division of Cardiology, Department of Medicine, Columbia University Medical Center and NewYork-Presbyterian Hospital, New York, New York; Department of Radiology, Columbia University Medical Center and NewYork-Presbyterian Hospital, New York, New York.
Andrew J
AJ
Einstein
Division of Cardiology, University of Kansas Medical Center, Kansas City, Kansas.
Ajay
A
Vallakati
Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Armin
A
Arbab-Zadeh
Division of Endocrinology, Department of Medicine, Columbia University Medical Center, New York, New York.
Marcella Donovan
MD
Walker
Division of Cardiology, Texas Tech University, El Paso, Texas.
Debabrata
D
Mukherjee
Division of Statistics, Maimonides Medical Center, Brooklyn, New York.
Peter
P
Homel
Division of Cardiovascular Medicine and The Howard Gilman Institute for Heart Valve Disease, State University of New York Downstate Medical Center, Brooklyn, New York.
Jeffrey S
JS
Borer
Department of Medicine, Maimonides Medical Center, Brooklyn, New York.
Edgar
E
Lichstein
D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000453:epidemiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D014943:Global Health; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D010024:Osteoporosis / Q000188:drug therapy; D012307:Risk Factors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates