Although opioids continue to be used internationally for noncancer pain, evidence to date on the comparative safety of different opioids is sparse and conflicting. The aim of this study was to examine the comparative risk of all-cause mortality in patients newly initiated on opioids for noncancer pain, across 3 jurisdictions in the United Kingdom (UK), United States, and Canada. A multicentre retrospective, population-based cohort study was conducted. Data sources included UK national primary care electronic health records (Clinical Practice Research Datalink), The Partners HealthCare Research Patient Data in Boston (US), and The Montreal Population Health Record data (Canada). New users of opioids aged ≥18 years without cancer were included. Patients with a diagnosis of a pain condition and with known back pain were analysed separately. Fully adjusted hazard ratios (HRs) were calculated using Cox-proportional models and adjusted for confounders. In total, 1,066,216 patients were included (UK: n = 993,294; Boston, US: n = 43,243; Montreal, Canada: n = 26,116). Compared with codeine, patients using morphine had a significantly higher adjusted risk in the UK {HR: 12.58 [95% confidence interval (CI), 11.87-13.32]}, US (HR: 8.62 [95% CI, 3.34-22.27]), and Canadian cohorts (HR: 6.69; [95% CI, 1.35-32.22]). In addition, other factors associated with higher mortality were being on combination opioids, fentanyl, buprenorphine, and oxycodone. Compared with those on <50 morphine milligram equivalents/day, patients on higher-doses experience an incremental increase in risk. In new users of opioids, compared with codeine, strong opioids, including morphine, fentanyl, buprenorphine, oxycodone, and combination opioids, and those on ≥50 morphine milligram equivalent/day were associated with a higher subsequent risk of all-cause mortality.

中文翻译：

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治疗非癌性疼痛的处方阿片类药物新使用者的死亡风险比较：国际药物监测研究的结果。


尽管阿片类药物在国际上继续用于治疗非癌性疼痛，但迄今为止关于不同阿片类药物的相对安全性的证据很少且相互矛盾。本研究的目的是检查在英国 （UK）、美国和加拿大的 3 个司法管辖区新开始使用阿片类药物治疗非癌性疼痛的患者全因死亡的比较风险。进行了一项多中心回顾性、基于人群的队列研究。数据来源包括英国国家初级保健电子健康记录（临床实践研究数据链）、波士顿（美国）的 The Partners HealthCare Research 患者数据以及蒙特利尔人口健康记录数据（加拿大）。纳入了年龄在 ≥18 岁无癌症的阿片类药物的新使用者。分别分析诊断为疼痛状况和已知背痛的患者。使用 Cox 比例模型计算完全调整的风险比 （HRs），并针对混杂因素进行调整。总共纳入了 1,066,216 名患者 （英国： n = 993,294;美国波士顿：n = 43,243;加拿大蒙特利尔：n = 26,116）。与可待因相比，使用吗啡的患者在英国 {HR： 12.58 [95% 置信区间 （CI）， 11.87-13.32]}、美国 （HR： 8.62 [95% CI， 3.34-22.27]） 和加拿大队列 （HR： 6.69;[95% CI，1.35-32.22]）。此外，与较高死亡率相关的其他因素是联合阿片类药物、芬太尼、丁丙诺啡和羟考酮。与服用 <50 毫克吗啡当量/天的患者相比，服用较高剂量的患者风险逐渐增加。 在阿片类药物的新使用者中，与可待因相比，强阿片类药物，包括吗啡、芬太尼、丁丙诺啡、羟考酮和联合阿片类药物，以及服用 ≥50 毫克吗啡当量/天的患者与更高的全因死亡后续风险相关。