Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
ICES, Toronto, ON, Canada.
Drugs Aging. 2022 Sep;39(9):729-738. doi: 10.1007/s40266-022-00970-x. Epub 2022 Aug 10.
Co-prescription of opioids with other central nervous system (CNS) depressants is common but the combination may increase the risk for adverse events such as falls and fractures, particularly among older adults. We explored the risk of fall- or fracture-related hospital visits after opioid initiation among older adults with varying degrees of concomitant CNS depressant burden.
We used population-based administrative health data from Ontario, Canada, to examine the relationship between hospital visits for falls or fractures at different levels of CNS burden among individuals aged 66 and older who started prescription opioids between March 1, 2008, and March 31, 2019. For comparison, we identified individuals starting prescription non-steroidal anti-inflammatory drugs (NSAIDs). The outcome was a hospital visit for falls or fractures within 14 days after starting analgesic therapy. We stratified the cohort according to additional CNS burden: none, low (one concurrent CNS depressant drug class) and high (≥ 2 concurrent CNS depressant classes) on the index date. We balanced opioid and NSAID recipients using inverse probability of treatment weighting and reported weighted hazard ratios from Cox proportional hazards models. We then used pairwise comparisons to determine differences between hazard ratios at different levels of CNS burden.
The cohort included 1,066,692 older adults, with 562,692 new opioid recipients and 504,000 new NSAID recipients. Among opioid recipients, 83 % had no additional CNS burden, 13 % had low burden and 4 % had high burden. The short-term rate of falls or fractures for new opioid recipients increased by CNS burden from 97 per 1000 person-years (no burden) to 233 per 1000 person-years (high CNS burden). Opioid recipients had a similarly elevated hazard of falls or fractures within each CNS burden level compared to NSAID recipients (adjusted hazard ratio [aHR] 1.62, 95 % CI 1.50-1.76 for no burden; aHR 1.69, 95 % CI 1.45-1.97 for low burden; aHR 1.40, 95 % CI 1.08-1.82 for high burden).
Among older adults, initiation of opioids is associated with an increased hazard of falls; however, this hazard is not modified by different levels of CNS depressant burden. This suggests that it remains important for physicians, patients, and caregivers to be vigilant when starting new opioid therapy regardless of other CNS medications taken concurrently.
阿片类药物与其他中枢神经系统(CNS)抑制剂的联合处方很常见,但这种联合用药可能会增加跌倒和骨折等不良事件的风险,尤其是在老年人中。我们探讨了在不同程度同时使用 CNS 抑制剂的老年患者中,开始使用阿片类药物后与跌倒或骨折相关的住院就诊风险。
我们使用加拿大安大略省的基于人群的行政健康数据,检查了在 2008 年 3 月 1 日至 2019 年 3 月 31 日期间开始使用处方阿片类药物的年龄在 66 岁及以上的个体中,不同 CNS 负担水平下与跌倒或骨折相关的住院就诊之间的关系。为了进行比较,我们确定了开始使用处方非甾体抗炎药(NSAIDs)的个体。结果是在开始镇痛治疗后 14 天内发生跌倒或骨折的住院就诊。我们根据指数日期的额外 CNS 负担将队列分层:无(一种同时使用的 CNS 抑制剂药物类别)、低(≥ 2 种同时使用的 CNS 抑制剂药物类别)和高(≥ 2 种同时使用的 CNS 抑制剂药物类别)。我们使用逆概率治疗加权法平衡了阿片类药物和 NSAID 接受者,并从 Cox 比例风险模型报告了加权风险比。然后,我们使用两两比较来确定不同 CNS 负担水平下风险比之间的差异。
该队列包括 1,066,692 名老年人,其中 562,692 名新阿片类药物接受者和 504,000 名新 NSAID 接受者。在阿片类药物接受者中,83%没有其他 CNS 负担,13%有低负担,4%有高负担。新阿片类药物接受者的短期跌倒或骨折发生率随着 CNS 负担的增加而增加,从无负担的每 1000 人年 97 例增加到高 CNS 负担的每 1000 人年 233 例。与 NSAID 接受者相比,在每个 CNS 负担水平下,阿片类药物接受者的跌倒或骨折风险也同样升高(无负担时调整后的危险比[aHR]为 1.62,95%CI 为 1.50-1.76;低负担时为 aHR 1.69,95%CI 为 1.45-1.97;高负担时为 aHR 1.40,95%CI 为 1.08-1.82)。
在老年人中,开始使用阿片类药物与跌倒风险增加相关;然而,不同程度的 CNS 抑制剂负担并不能改变这种风险。这表明,无论同时服用其他 CNS 药物如何,医生、患者和护理人员在开始新的阿片类药物治疗时都应保持警惕,这一点仍然很重要。