Fung Kin Wah, Baye Fitsum, Kapusnik-Uner Joan, McDonald Clement J
Lister Hill National Center for Biomedical Communications, National Library of Medicine, U.S. National Institutes of Health, 8600 Rockville Pike, Bethesda, MD, 20894, USA.
First Databank. Inc., San Francisco, CA, USA.
Drugs Real World Outcomes. 2021 Jun;8(2):173-185. doi: 10.1007/s40801-021-00230-1. Epub 2021 Feb 10.
Serious cardiac arrhythmias caused by QT-prolonging drugs are difficult to predict based on physiological measurement and pre-approval clinical trials. Post-marketing surveillance and monitoring are important to generate safety data.
To assess whether an observational study using Medicare claims data can detect the arrhythmogenic risk of QT-prolonging drugs.
We identified 17 QT-prolonging drugs with known risk of torsades des pointes (TdP) that were not used to treat cardiac arrhythmias. Amoxicillin and four serotonin-norepinephrine reuptake inhibitors (SNRIs) were used as controls. De-identified claims data of 1.2 million Medicare beneficiaries were accessed. Two separate Cox regressions were done for short-term and chronic-use drugs. The primary outcome was a composite of ventricular arrhythmias and/or sudden death, identified by ICD diagnostic codes. We explored the independent effect of each study drug on the outcomes. Other covariates included patient demographics, comorbidities, and known risk factors for drug-induced cardiac arrhythmia.
We were able to detect increased risk in 14 of 17 study drugs (82.3%), and none of the control drugs. Among the fluoroquinolones, ciprofloxacin was the safest. Azithromycin and clarithromycin were relatively safe compared to erythromycin. Compared to SNRIs, both citalopram and escitalopram had increased risk, more so with escitalopram than citalopram. Comorbidities associated with increased risk included ischemic heart disease, electrolyte imbalance, bradycardia, acute myocardial infarction, heart failure, and chronic kidney and liver disease.
Medicare data can be utilized for post-marketing surveillance and monitoring of the proarrhythmic risk of QT-prolonging drugs in older adults.
基于生理测量和批准前的临床试验，很难预测由延长QT间期的药物引起的严重心律失常。上市后监测对于生成安全性数据很重要。
评估一项使用医疗保险索赔数据的观察性研究能否检测出延长QT间期药物的致心律失常风险。
我们识别出17种已知有致尖端扭转型室性心动过速（TdP）风险且不用于治疗心律失常的延长QT间期药物。阿莫西林和四种5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）用作对照。获取了120万医疗保险受益人的匿名索赔数据。对短期用药和长期用药的药物分别进行了两次Cox回归分析。主要结局是由国际疾病分类诊断代码确定的室性心律失常和/或猝死的复合结局。我们探究了每种研究药物对结局的独立影响。其他协变量包括患者人口统计学特征、合并症以及药物性心律失常的已知风险因素。
我们能够在17种研究药物中的14种（82.3%）中检测到风险增加，而对照药物均未出现这种情况。在氟喹诺酮类药物中，环丙沙星是最安全的。与红霉素相比，阿奇霉素和克拉霉素相对安全。与SNRIs相比，西酞普兰和艾司西酞普兰的风险均增加，且艾司西酞普兰的风险增加幅度大于西酞普兰。与风险增加相关的合并症包括缺血性心脏病、电解质失衡、心动过缓、急性心肌梗死、心力衰竭以及慢性肾脏和肝脏疾病。
医疗保险数据可用于对老年人中延长QT间期药物的促心律失常风险进行上市后监测。
