Optum, 1325 Boylston Street, Boston, MA, 02215, USA.
University of Southern Denmark, Odense, Denmark.
Drug Saf. 2021 Aug;44(8):899-915. doi: 10.1007/s40264-021-01095-7. Epub 2021 Jul 8.
During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder.
The purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use.
We conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012-December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated.
Overall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73-0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76-0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings.
This large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.
在临床试验中，β3 肾上腺素能受体激动剂米拉贝隆与安慰剂相比，可使膀胱过度活动症患者的生命体征升高。
本研究旨在比较米拉贝隆或抗毒蕈碱药物使用后不良心血管（CV）结局的发生率。
我们利用真实世界的数据进行了一项观察性上市后安全性研究。研究人群在五个来源中确定：丹麦和瑞典国家登记处、临床实践研究数据链接（英国）、Optum（美国）和 Humana（美国）。从处方中获取患者新使用米拉贝隆或抗毒蕈碱药物（2012 年 10 月至 2018 年 12 月）的时段，并根据倾向评分进行匹配。确定主要不良心血管事件（MACE）、急性心肌梗死（AMI）、中风、心血管死亡率和全因死亡率的发生情况。使用 Cox 模型估计结局发生率和风险比。
总体而言，匹配了 152026 例米拉贝隆和 152026 例抗毒蕈碱药物的发作。该人群中 63.1%为女性，72.6%年龄≥65 岁。米拉贝隆和抗毒蕈碱药物使用者的 MACE、AMI 或中风发生率无明显差异。心血管死亡率（风险比 0.83，95%置信区间 0.73-0.95）和全因死亡率（风险比 0.80，95%置信区间 0.76-0.84）的发生率均不高于米拉贝隆。将结果限制在心血管事件风险较高的发作中，或根据年龄（<65 岁，≥65 岁）或既往膀胱过度活动症药物使用进行分层，结果与总体发现一致。
这项大型的多国研究发现，与抗毒蕈碱药物相比，米拉贝隆使用者发生 MACE、AMI、中风、心血管死亡率或全因死亡率的风险没有增加。
