School of Pharmacy, Department of Clinical Sciences, Medical College of Wisconsin, Milwaukee.
Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina.
JAMA Netw Open. 2020 Sep 1;3(9):e2016858. doi: 10.1001/jamanetworkopen.2020.16858.
National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population.
To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020.
Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims.
Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics.
Among 38 310 women included in the study (mean [SD] age, 74.3 [6.3] years), there were 0.010 (95% CI, 0.008-0.011) adverse drug events related to substance misuse per 1000 person-days, 0.237 (95% CI, 0.229-0.245) other adverse drug events associated with opioid use per 1000 person-days, and 0.675 (95% CI, 0.662-0.689) all-cause hospitalizations per 1000 person-days. Opioid use was associated with increased risk of adverse drug events related to substance misuse (aRR, 14.62; 95% CI, 9.69-22.05; P < .001), other adverse drug events related to opioid use (aRR, 2.50; 95% CI, 2.11-2.96; P < .001), and all-cause hospitalization (aRR, 2.77; 95% CI, 2.55-3.02; P < .001). In a dose-response effect, individuals with high daily opioid doses had consistently higher risks of all study outcomes compared with individuals who had low opioid doses. Compared with days with no opioid exposure, the risk of any adverse drug event related to substance misuse was 3.4-fold higher for individuals with a current opioid supply ≥50 mg morphine equivalent dose per day (aRR, 3.40; 95% CI, 2.47-4.68; P < .001), while the risk was 2.3-fold higher for individuals with 1 to 49 mg morphine equivalent dose per day (aRR, 2.29; 95% CI, 1.89-2.77; P < .001).
These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy.
国家提高安全阿片类药物处方的努力重点是预防误用、过量和阿片类药物使用障碍。这种方法忽略了在复杂人群中更好地预防其他严重的与阿片类药物相关的伤害的机会，如癌症幸存者的老年人。对于这一人群中与阿片类药物相关的全面伤害的发生率和风险因素知之甚少。
确定在接受乳腺癌治疗后幸存的老年患者中发生多种与阿片类药物相关的不良药物事件的发生率，并估计在完成癌症治疗后的一年内使用阿片类药物与这些事件发生的风险。
设计、地点和参与者：这项回顾性队列研究使用了 2007 年至 2016 年医疗保险服务（Medicare）的监测、流行病学和最终结果（Surveillance, Epidemiology and End Results）-医疗保险数据，纳入了 2008 年 1 月 1 日至 2015 年 12 月 31 日期间年龄在 66 至 90 岁之间、患有 0 至 III 期乳腺癌的第一癌症诊断的自付费 Medicare 受益人，这些患者完成了积极的乳腺癌治疗。数据于 2019 年 10 月 31 日至 2020 年 6 月 10 日进行了分析。
重复的每日测量指标，表示在 Medicare 部分 D 处方索赔中拥有任何处方阿片类药物供应。
使用修正泊松广义估计方程模型，估计与物质滥用相关的不良药物事件（即诊断为阿片类药物滥用、依赖或中毒）、与阿片类药物使用相关的其他不良药物事件（即胃肠道事件、感染、跌倒和骨折或心血管事件）以及前一天阿片类药物供应相关的全因住院的调整风险比（aRR），控制患者特征。
在纳入的 38310 名女性患者中（平均[标准差]年龄为 74.3[6.3]岁），每 1000 人天发生 0.010（95%CI，0.008-0.011）例与物质滥用相关的不良药物事件，每 1000 人天发生 0.237（95%CI，0.229-0.245）例与阿片类药物使用相关的其他不良药物事件，以及每 1000 人天发生 0.675（95%CI，0.662-0.689）例全因住院。阿片类药物的使用与与物质滥用相关的不良药物事件（aRR，14.62；95%CI，9.69-22.05；P<0.001）、与阿片类药物使用相关的其他不良药物事件（aRR，2.50；95%CI，2.11-2.96；P<0.001）和全因住院（aRR，2.77；95%CI，2.55-3.02；P<0.001）的风险增加相关。在剂量反应效应中，与使用低剂量阿片类药物的个体相比，高剂量阿片类药物的个体所有研究结果的风险始终更高。与无阿片类药物暴露的天数相比，当前阿片类药物供应≥50mg 吗啡当量剂量/天的个体发生任何与物质滥用相关的不良药物事件的风险高 3.4 倍（aRR，3.40；95%CI，2.47-4.68；P<0.001），而每天使用 1 至 49mg 吗啡当量剂量的个体风险高 2.3 倍（aRR，2.29；95%CI，1.89-2.77；P<0.001）。
这些发现表明，在接受乳腺癌治疗后幸存的老年人中，在完成积极的癌症治疗后的一年内继续开具处方阿片类药物与广泛的与物质滥用相关的严重不良药物事件和其他与阿片类药物使用相关的不良药物事件的即时风险增加相关。临床医生应考虑使用长期阿片类药物治疗管理癌症疼痛的全面风险。
