OPEN, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
Novartis Healthcare Pvt. Ltd., Hyderabad, India.
Bone. 2020 May;134:115296. doi: 10.1016/j.bone.2020.115296. Epub 2020 Feb 22.
This observational safety study used national registers to compare the real world cardiovascular and skeletal safety of zoledronic acid (ZA) against oral bisphosphonates (oBP) and untreated population controls.
Propensity score matched cohort study in Sweden and Denmark.
Matched cohort 1 included 8739 ZA users and 25,577 oBP users while matched cohort 2 included 8731 ZA users and 25,924 untreated subjects. In comparison to oBP users, heart failure risk was higher in ZA users, with an adjusted HR (adj) (95%CI) of 1.17 (1.04;1.32) and a higher all-cause mortality (adj HR 1.24 (1.15; 1.34)), however, there was no increased risk of cardiovascular mortality. In the comparison to untreated subjects, ZA users showed a higher risk of atrial fibrillation, adj HR 1.18 (1.05;1.32), arrhythmias adj HR 1.18 (1.06;1.31), and heart failure, adj HR 1.38 (1.24;1.54). Cardiovascular mortality was lower in ZA users (adj HR 0.87 (0.77; 0.98)) and risk of adverse skeletal outcomes was significantly higher, reflecting more severe osteoporosis in these patients. There was no association of cardiovascular risk with increasing exposure time. Sensitivity analyses produced similar findings with no substantial changes in event rates.
We noted an increased risk of heart failure, fractures and death among ZA users compared with oral BP. The risk of cardiovascular and skeletal outcomes was higher in ZA users than in matched population controls, but there was no increase in cardiovascular mortality in ZA users compared to oral BP or untreated controls. Despite propensity score matching, it is not possible to determine with certainty whether the increased risk of cardiovascular outcomes is consistent with a true drug effect or higher baseline risk in patients who begin ZA treatment.
本观察性安全性研究利用国家登记处，比较唑来膦酸（ZA）与口服双膦酸盐（oBP）和未治疗人群对照的真实世界心血管和骨骼安全性。
在瑞典和丹麦进行倾向评分匹配队列研究。
匹配队列 1 纳入 8739 例 ZA 使用者和 25577 例 oBP 使用者，匹配队列 2 纳入 8731 例 ZA 使用者和 25924 例未治疗患者。与 oBP 使用者相比，ZA 使用者心力衰竭风险更高，校正后 HR（adj）（95%CI）为 1.17（1.04；1.32），全因死亡率更高（adj HR 1.24（1.15；1.34）），但心血管死亡率无增加风险。与未治疗患者相比，ZA 使用者发生心房颤动的风险更高，adj HR 1.18（1.05；1.32），心律失常 adj HR 1.18（1.06；1.31），心力衰竭 adj HR 1.38（1.24；1.54）。ZA 使用者心血管死亡率较低（adj HR 0.87（0.77；0.98）），不良骨骼结局风险显著升高，反映这些患者骨质疏松更严重。心血管风险与暴露时间的增加无关。敏感性分析得出的结果相似，事件发生率无实质性变化。
与口服 BP 相比，我们注意到 ZA 使用者心力衰竭、骨折和死亡的风险增加。ZA 使用者的心血管和骨骼结局风险高于匹配的人群对照，但与口服 BP 或未治疗对照相比，ZA 使用者的心血管死亡率没有增加。尽管进行了倾向评分匹配，但仍不能确定心血管结局风险的增加是否与药物的真实作用或开始 ZA 治疗的患者的基线风险较高相一致。
