Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis

Chest. 2013 Oct;144(4):1311-1322. doi: 10.1378/chest.13-0675.


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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Atrial Fibrillation / chemically induced*
  • Bone Density Conservation Agents / adverse effects*
  • Diphosphonates / adverse effects*
  • Humans
  • Risk Assessment
  • Severity of Illness Index
  • Stroke / chemically induced*


  • Bone Density Conservation Agents
  • Diphosphonates