英国牛津大学Daniel Prieto-Alhambra团队研究了曲马多与可待因处方配伍与死亡率和其他不良临床结局的相关性。相关论文于2021年10月19日发表于《美国医学会杂志》。

尽管曲马多越来越多地用于治疗慢性非癌症疼痛，但很少有安全性研究将其与其他阿片类药物进行比较。

为了评估与可待因相比，曲马多与门诊患者的死亡率和其他不良临床结局的相关性，研究组将回顾性、基于人群的倾向评分匹配队列研究，使用初级保健数据库，常规收集医疗记录和药房处方，覆盖西班牙加泰罗尼亚80%以上的人口（≈600万人）。

纳入18岁及以上、且有1年及以上可用数据和曲马多或可待因处方（2007-2017年）的患者，并随访至2017年12月31日。暴露因素为曲马多或可待因的新处方。研究结局为首次用药后1年内的全因死亡、心血管事件、骨折、便秘、谵妄、跌倒、阿片类药物滥用/依赖和睡眠障碍。

1093064名患者在研究期间服用曲马多或可待因，其中326921名服用曲马多，762492?名服用可待因，3651例两种药物合用。共368960名患者（184480对倾向评分匹配）?纳入研究，平均年龄为53.1岁，57.3%为女性。与可待因相比，曲马多处方与全因死亡、心血管事件和骨折的高风险显著相关。但与跌倒、谵妄、便秘、阿片类药物滥用/依赖或睡眠障碍的风险无关。

在这项基于人群的队列研究中，与可待因相比，曲马多的新处方与后续全因死亡、心血管事件和骨折的高风险显著相关，但便秘、谵妄、跌倒、阿片类药物滥用/依赖或睡眠障碍的风险无显著差异。

附：英文原文

Title: Association of Tramadol vs Codeine Prescription Dispensation With Mortality and Other Adverse Clinical Outcomes

Author: Junqing Xie, Victoria Y. Strauss, Daniel Martinez-Laguna, Cristina Carbonell-Abella, Adolfo Diez-Perez, Xavier Nogues, Gary S. Collins, Sara Khalid, Antonella Delmestri, Aleksandra Turkiewicz, Martin Englund, Mina Tadrous, Carlen Reyes, Daniel Prieto-Alhambra

Issue&Volume: 2021/10/19

Abstract:

Importance  Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids.

Objective  To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings.

Design, Setting, and Participants  Retrospective, population-based, propensity score–matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017.

Exposures  New prescription dispensation of tramadol or codeine (no dispensation in the previous year).

Main Outcomes and Measures  Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models.

Results  Of the 1093064 patients with a tramadol or codeine dispensation during the study period (326921 for tramadol, 762492 for codeine, 3651 for both drugs concomitantly), a total of 368960 patients (184480 propensity score–matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders.

Conclusions and Relevance  In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding.

DOI: 10.1001/jama.2021.15255

Source: https://jamanetwork.com/journals/jama/article-abstract/2785265