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.