Atrial fibrillation in patients treated with intravenous zoledronic or pamidronic acid: A pharmacoepidemiological study

Abstract

Objective: Atrial fibrillation (AF) may be triggered by intravenous bispho sphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the associ ation between AF and IVBPs in a real-life large pharmacovigilance database. Design: A systematic analysis of VigiBase, the World Health Organizati on's pharmacovigilance database. Methods: Analysis of adverse events reported as 'atrial fibrillation' (a ccording to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic ac id or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) data base. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality a nalysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0. Results: 530 ICSRs reporting on the association between AF and IVBPs we re extracted. Bayesian disproportionality analysis detected a significant association between AF and use o f zoledronic acid (IC025 = 1.83) and pamidronic acid (IC025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI : 1.17-7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender. Conclusions: This is the first VigiBase pharmacoepidemiological study confirm ing the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcom e. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.