Oregon Research Institute, Eugene, OR, USA.
School of Nursing, Virginia Commonwealth University, Richmond, VA, USA.
Drugs Aging. 2022 May;39(5):377-387. doi: 10.1007/s40266-022-00941-2. Epub 2022 May 20.
Limited evidence for incident frailty risks associated with prescription analgesics and sedatives in older (≥ 65 years) community-living adults prompted a more comprehensive investigation.
We used data from older Health and Retirement Study respondents and three frailty models (frailty index, functional domain, frailty phenotype with 8803, 10,470, and 6850 non-frail individuals, respectively) and estimated sub-hazard ratios of regular prescription drug use (co-use, analgesic use, and sedative use), by frailty model. We addressed confounding with covariate adjustment and propensity score matching approaches.
The baseline prevalence of analgesic and sedative co-use, analgesic use, and sedative use among non-frail respondents was 1.8%, 12.8%, and 4.7% for the frailty index model, 4.2%, 16.2%, and 5.3% for the functional domain model, and 4.3%, 15.4%, and 6.1% for the frailty phenotype model, respectively. Cumulative frailty incidence over 10 years was 39.3%, 36.1%, and 14.2% for frailty index, functional domain, and frailty phenotype models, respectively; covariate-adjusted sub-hazard ratio estimates were 2.00 (1.63-2.45), 1.83 (1.57-2.13), and 1.68 (1.21-2.33) for co-use; 1.72 (1.56-1.89), 1.38 (1.27-1.51), and 1.51 (1.27-1.79) for analgesic use; and 1.46 (1.24-1.72), 1.25 (1.07-1.46), and 1.31 (0.97-1.76) for sedative use. Frailty risk ranking (co-use > analgesic use > sedative use) persisted across all model sensitivity analyses.
Consistently significant frailty risk estimates of regular prescription analgesic and sedative co-use and of prescription analgesic use support existing clinical, public health, and regulatory guidance on opioid and benzodiazepine co-prescription, on opioid prescription, and on NSAID prescription. Frailty phenotype measurement administration limited power to detect significant frailty risks. Research into specific pharmaceutical exposures and comparison of results across cohorts will be required to contribute to the deprescribing evidence base.
在年龄较大（≥65 岁）的社区居住成年人中，与处方止痛药和镇静剂相关的偶发性虚弱风险的证据有限，这促使我们进行了更全面的调查。
我们使用了来自年龄较大的健康与退休研究受访者的数据和三种虚弱模型（虚弱指数、功能域和 8803、10470 和 6850 名非虚弱个体的虚弱表型），并通过虚弱模型估计了定期使用处方药（联合使用、使用止痛药和使用镇静剂）的亚危险比。我们通过协变量调整和倾向评分匹配方法解决了混杂因素。
在非虚弱受访者中，虚弱指数模型、功能域模型和虚弱表型模型的基线时，联合使用止痛药和镇静剂、使用止痛药和使用镇静剂的发生率分别为 1.8%、12.8%和 4.7%、4.2%、16.2%和 5.3%、4.3%、15.4%和 6.1%。10 年内累积虚弱发生率分别为虚弱指数、功能域和虚弱表型模型的 39.3%、36.1%和 14.2%；经协变量调整后的亚危险比估计值分别为 2.00（1.63-2.45）、1.83（1.57-2.13）和 1.68（1.21-2.33）用于联合使用；1.72（1.56-1.89）、1.38（1.27-1.51）和 1.51（1.27-1.79）用于使用止痛药；以及 1.46（1.24-1.72）、1.25（1.07-1.46）和 1.31（0.97-1.76）用于使用镇静剂。在所有模型敏感性分析中，规律使用处方止痛药和镇静剂联合使用以及使用止痛药的虚弱风险排名（联合使用>使用止痛药>使用镇静剂）保持一致。
定期使用处方止痛药和镇静剂联合使用以及使用止痛药的显著虚弱风险估计值，支持了关于阿片类药物和苯二氮䓬类药物联合处方、阿片类药物处方和非甾体抗炎药处方的现有临床、公共卫生和监管指南。虚弱表型测量的管理限制了检测显著虚弱风险的能力。需要对特定药物暴露进行研究，并对队列结果进行比较，以丰富停药证据基础。
