Bisphosphonates and risk of atrial fibrillation: a meta-analysis

INTRODUCTION Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Although a recent FDA review of the results of clinical trials reported no clear link between bisphosphonates and serious or non-serious atrial fibrillation (AF), some epidemiologic studies have suggested an association between AF and bisphosphonates. METHODS We conducted a meta-analysis of non-experimental studies to evaluate the risk of AF associated with bisphosphonates. Studies were identified by searching MEDLINE and EMBASE using a combination of the Medical Subject Headings and keywords. Our search was limited to English language articles. The pooled estimates of odds ratios (OR) as a measure of effect size were calculated using a random effects model. RESULTS Seven eligible studies with 266,761 patients were identified: three cohort, three case-control, and one self-controlled case series. Bisphosphonate exposure was not associated with an increased risk of AF [pooled multivariate OR 1.04, 95% confidence interval (CI) 0.92-1.16] after adjusting for known risk factors. Moderate heterogeneity was noted (I-squared score = 62.8%). Stratified analyses by study design, cohort versus case-control studies, yielded similar results. Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively). No clear asymmetry was observed in the funnel plot analysis. Few studies compared risk between bisphosphonates or by dosing. CONCLUSIONS Our study did not find an association between bisphosphonate exposure and AF. This finding is consistent with the FDA's statement.