目标:2022年,超过109,000名美国人死于药物过量,其中81,231例过量死亡涉及阿片类药物。美沙酮,丁丙诺啡和纳曲酮是阿片类药物使用障碍(MOUD)使用最广泛的药物,也是预防过量死亡的最有效干预措施.然而,有人担心美沙酮会导致长QT综合征,这增加了致命的心律失常的风险。目前,很少有研究系统地评估MOUD之间心脏和死亡率结果的短期和长期差异。
目的:为了比较心律失常的风险,服用美沙酮的阿片类药物使用障碍(OUD)患者之间的长QT综合征和总死亡率,丁丙诺啡或纳曲酮。
方法:基于美国多中心和全国性电子健康记录(EHRs)数据库的回顾性队列研究。研究人群由144,141名患者组成,他们在2016-2022年因OUD就诊,在进行OUD诊断后1个月内接受了MOUD处方,并且在任何MOUD处方之前均未诊断出心律失常或长QT综合征。研究人群分为三个队列:(1)美沙酮队列(n=40,938)-仅服用美沙酮。(2)丁丙诺啡队列(n=80,055)-仅服用丁丙诺啡。(3)纳曲酮队列(n=5,738)-仅服用纳曲酮。
方法:美沙酮,丁丙诺啡,或者纳曲酮.
方法:心律失常,长QT综合征,和死亡。在六个不同的随访时间框架(1个月,3个月,6个月,1年,3年,和5年),通过使用Kaplan-Meier生存分析比较倾向评分匹配的队列。
结果:服用美沙酮的OUD患者发生心律失常的风险明显较高,与使用丁丙诺啡或纳曲酮的OUD患者的倾向评分相匹配的患者相比,长QT综合征和死亡。对于1个月的随访,在美沙酮队列中,心律失常的总体风险为1.03%,高于匹配的丁丙诺啡队列中的0.87%(HR:1.20,95%CI:1.04-1.39);美沙酮队列中长QT综合征的总体风险为0.35%,高于匹配的丁丙诺啡队列中的0.15%(HR:2.40,95%CI:1.75-3.28);美沙酮队列中的总死亡率为0.59%,高于匹配的丁丙诺啡队列中的0.41%(HR:1.48,95%CI:1.21-1.81)。增加的风险持续5年:心律失常(HR:1.31,95%CI:1.23-1.38),长QT综合征(HR:3.14,95%CI:2.76-3.58),死亡(HR:1.50,95%CI:1.41-1.59)。
结论:与丁丙诺啡和纳曲酮相比,美沙酮与心脏病和死亡结局的风险显著相关。这些发现与启动MOUD治疗时药物选择指南的制定有关,并为OUD的未来药物开发提供信息,以最大限度地降低风险,同时最大限度地提高收益。
More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD.
To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone.
Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone.
methadone, buprenorphine, or naltrexone.
Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis.
Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59).
Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.