Departments of Medicine and Pharmacology (CPC, KTM, CMS), Biostatistics (WDD), and Health Policy (KH, WAR), Vanderbilt University Medical Center, United States.
Pharmacoepidemiol Drug Saf. 2019 Jan;28(1):48-53. doi: 10.1002/pds.4619. Epub 2018 Jul 12.
Despite significant growth of opioid prescriptions, only limited data are available regarding the comparative safety of long-acting opioids for chronic non-cancer pain. Recent data suggest that transdermal fentanyl and oxycodone CR may have greater toxicity than morphine SR in patients with non-cancer pain. Thus, we compared the risk of out-of-hospital deaths in patients with non-cancer pain filling prescriptions for transdermal fentanyl or oxycodone CR with that for morphine SR.
We conducted a retrospective cohort study in 50 658 patients enrolled in Tennessee Medicaid who filled prescriptions for transdermal fentanyl (n = 8717), oxycodone CR (n = 14 118), or morphine SR (n = 27 823) between 1999 and 2011. We excluded individuals with cancer or other life-threatening diagnoses and used propensity scores to adjust for multiple potential confounders. The primary outcome was out-of-hospital mortality.
During 44 385 person-years of follow-up, 689 patients died. The out-of-hospital mortality rate among all study subjects was 155/10 000 patient-years. Contrary to earlier data suggesting greater risk, mortality was not significantly different in patients filling prescriptions for transdermal fentanyl compared with morphine SR (adjusted HR = 0.96, 95% C.I.: 0.77-1.21); moreover, patients filling prescriptions for oxycodone CR had lower mortality risk compared with those filling prescriptions for morphine SR (adjusted HR = 0.79, 95% C.I. 0.66-0.95).
In the study population, long-acting opioids for non-cancer pain were associated with high out-of-hospital mortality rates. We found comparable out-of-hospital mortality risks associated with transdermal fentanyl and morphine SR. The risk of out-of-hospital death for oxycodone CR was lower than that for morphine SR.
尽管阿片类药物处方量显著增加,但关于长期阿片类药物治疗慢性非癌痛的相对安全性的数据仍十分有限。最近的数据表明,对于患有非癌痛的患者,透皮芬太尼和羟考酮控释剂的毒性可能大于吗啡控释剂。因此,我们比较了患有非癌痛的患者使用透皮芬太尼或羟考酮控释剂与使用吗啡控释剂处方的院外死亡率。
我们对田纳西州医疗补助计划中 50658 名患者进行了回顾性队列研究,这些患者在 1999 年至 2011 年期间服用了透皮芬太尼(n=8717)、羟考酮控释剂(n=14118)或吗啡控释剂(n=27823)。我们排除了患有癌症或其他危及生命的诊断的患者,并使用倾向评分来调整多种潜在混杂因素。主要结局是院外死亡率。
在 44385 人年的随访期间,有 689 名患者死亡。所有研究对象的院外死亡率为 155/10000 人年。与早期数据表明的更高风险相反,与使用吗啡控释剂相比,使用透皮芬太尼处方的患者的死亡率并无显著差异(调整后的 HR=0.96,95%CI:0.77-1.21);此外,与使用吗啡控释剂处方的患者相比,使用羟考酮控释剂处方的患者的死亡率风险更低(调整后的 HR=0.79,95%CI:0.66-0.95)。
在研究人群中,用于非癌痛的长效阿片类药物与高院外死亡率相关。我们发现,与透皮芬太尼和吗啡控释剂相比,院外死亡率的风险相当。羟考酮控释剂的院外死亡风险低于吗啡控释剂。