Solomon Daniel H, Rassen Jeremy A, Glynn Robert J, Garneau Katie, Levin Raisa, Lee Joy, Schneeweiss Sebastian
Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Arch Intern Med. 2010 Dec 13;170(22):1979-86. doi: 10.1001/archinternmed.2010.450.
Severe nonmalignant pain affects a large proportion of adults. Optimal treatment is not clear, and opioids are an important option for analgesia. However, there is relatively little information about the comparative safety of opioids. Therefore, we sought to compare the safety of opioids commonly used for nonmalignant pain.
We devised a propensity-matched cohort analysis that used health care utilization data collected from January 1, 1996, through December 31, 2005. Study participants were Medicare beneficiaries from 2 US states who were new initiators of opioid therapy for nonmalignant pain, including codeine phosphate, hydrocodone bitartrate, oxycodone hydrochloride, propoxyphene hydrochloride, and tramadol hydrochloride; none had a cancer diagnosis, and none were using hospice or nursing home care. Our main outcome measures were incidence rates and rate ratios (RRs) with 95% confidence intervals (CIs) for cardiovascular events, fractures, gastrointestinal events, and several composite end points.
We matched 6275 subjects in each of the 5 opioid groups. The groups were well matched on baseline characteristics. The risk of cardiovascular events was similar across opioid groups 30 days after the start of opioid therapy, but it was elevated for codeine (RR, 1.62; 95% CI, 1.27-2.06) after 180 days. Compared with hydrocodone, after 30 days of opioid exposure the risk of fracture was significantly reduced for tramadol (RR, 0.21; 95% CI, 0.16-0.28) and propoxyphene (0.54; 0.44-0.66) users. The risk of gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone (RR, 2.43; 95% CI, 1.47-4.00) and codeine (2.05; 1.22-3.45) users compared with hydrocodone users.
The rates of safety events among older adults using opioids for nonmalignant pain vary significantly by agent. Causal inference requires experimental designs, but these results should prompt caution and further study.
严重的非恶性疼痛影响着很大一部分成年人。最佳治疗方法尚不清楚，阿片类药物是镇痛的重要选择。然而，关于阿片类药物相对安全性的信息较少。因此，我们试图比较常用于非恶性疼痛的阿片类药物的安全性。
我们设计了一项倾向匹配队列分析，使用了1996年1月1日至2005年12月31日收集的医疗保健利用数据。研究参与者是来自美国两个州的医疗保险受益人，他们是新开始使用阿片类药物治疗非恶性疼痛的患者，包括磷酸可待因、氢可酮酒石酸盐、盐酸羟考酮、盐酸丙氧芬和盐酸曲马多；没有人被诊断患有癌症，也没有人使用临终关怀或养老院护理。我们的主要结局指标是心血管事件、骨折、胃肠道事件以及几个复合终点的发病率和率比（RR）及其95%置信区间（CI）。
我们在5个阿片类药物组中每组匹配了6275名受试者。各组在基线特征方面匹配良好。开始阿片类药物治疗30天后，各阿片类药物组中心血管事件的风险相似，但180天后可待因组的风险升高（RR，1.62；95%CI，1.27 - 2.06）。与氢可酮相比，在阿片类药物暴露30天后，曲马多使用者（RR，0.21；95%CI，0.16 - 0.28）和丙氧芬使用者（0.54；0.44 - 0.66）的骨折风险显著降低。各阿片类药物组之间胃肠道安全事件的风险没有差异。与氢可酮使用者相比，羟考酮使用者（RR，2.43；95%CI，1.47 - 4.00）和可待因使用者（2.05；1.22 - 3.45）在30天后全因死亡率升高。
使用阿片类药物治疗非恶性疼痛的老年人中，安全事件发生率因药物种类而异。因果推断需要实验设计，但这些结果应引起谨慎并促使进一步研究。
