Department of Rheumatology, Hôpitaux Universitaires de Strasbourg, Strasbourg University, Strasbourg, France.
Department of Pharmacology, AP-HP, Pitié-Salpêtrière Hospital, CIC-1421, Regional Pharmacovigilance Center INSERM, Sorbonne Universités, Paris, France.
Eur J Endocrinol. 2021 Mar;184(3):437-444. doi: 10.1530/EJE-20-0650.
Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a real-life large pharmacovigilance database.
A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database.
Analysis of adverse events reported as 'atrial fibrillation' (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0.
530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of 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.
This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.
静脉用双膦酸盐（IVBPs），如唑来膦酸或帕米膦酸，可能引发心房颤动（AF）。我们的目的是在真实的大型药物警戒数据库中确认 AF 与 IVBPs 之间的关联。
对世界卫生组织药物警戒数据库 VigiBase 进行系统分析。
分析与唑来膦酸或帕米膦酸使用相关的报告为“心房颤动”（根据药物监管活动医学词典）的不良事件，这些事件在世界卫生组织全球个体病例安全报告（ICSR）数据库 VigiBase 中。将所有报告与唑来膦酸或帕米膦酸相关的 AF 的 ICSR 纳入比例不平衡分析中，确定信息成分（IC025）的 95%置信区间下限，当>0 时显示出统计学关联。
提取了 530 份报告 AF 与 IVBPs 之间关联的 ICSR。贝叶斯比例不平衡分析检测到 AF 与唑来膦酸（IC025=1.83）和帕米膦酸（IC025=2.16）的使用之间存在显著关联。对这些 ICSR 的进一步分析确定，85.0%的情况下 AF 是严重的，死亡率为 17.7%。与帕米膦酸相比，唑来膦酸治疗后严重 AF 的风险增加（OR：2.98（95%CI：1.17-7.57），P=0.02），调整年龄和性别后。
这是第一项在 VigiBase 中进行的药物流行病学研究，证实了 IVBPs 与 AF 之间的关联。大多数 AF 是严重的，致死率很高。与帕米膦酸相比，唑来膦酸治疗后严重 AF 的风险增加，因此主张谨慎使用 IVBPs。
