PURPOSE:Bisphosphonates are commonly used drugs in clinical practice. The gastrointestinal adverse effects have been well documented, however little is known about the possible cardiovascular adverse effects. The aim of this report is to evaluate the relationship between bisphosphonates and atrial fibrillation (AF) in randomized clinical trials (RCT).
METHODS:We selected all studies in the English literature in which bisphosphonates were compared to placebo using a RCT design and reported AF as an adverse event. We calculated the pooled odds ratio (OR) with the corresponding 95% confidence interval (CI) for incident AF (AF) and serious AF (SAF) using the Peto fixed effects method. SAF was defined as an event that either resulted in hospitalization or death as opposed to any AF event. We used chi square to measure heterogeneity and Egger’s method to assess publication bias.
RESULTS:Our search strategy yielded 1646 studies; however, only three studies met our eligibility criteria. There was no evidence of publication bias (p=0.34). These included 16,322 patients of whom 76 to 100% were women using bisphosphonates for osteoporosis with a mean age that ranged from 69–75 years old. The studies included alendronate and zoledronic acid. The OR of incident AF was 1.19 (95% C.I. 0.97–1.46) for bisphosphonates compared to placebo. The OR of SAF was 1.68 (95% C.I. 1.23–2.29) for bisphosphonates compared to placebo (figure).
CONCLUSION:Bisphosphonates increase the risk of serious AF.
CLINICAL IMPLICATIONS:The mechanism, population at risk and the impact of this important adverse event should be further evaluated in studies and be weighed against the benefit of decreased fracture risk.
DISCLOSURE:Jennifer Miranda, No Financial Disclosure Information; No Product/Research Disclosure Information