Schöttker Ben, Saum Kai-Uwe, Muhlack Dana Clarissa, Hoppe Liesa Katharina, Holleczek Bernd, Brenner Hermann
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Network Aging Research, University of Heidelberg, Heidelberg, Germany.
Eur J Clin Pharmacol. 2017 Aug;73(8):1041-1048. doi: 10.1007/s00228-017-2266-7. Epub 2017 May 24.
The objective was to investigate whether the association of polypharmacy with non-cancer mortality is independent from comorbidity and is not a result of confounding by indication.
Analyses were conducted in 2687 participants of a German, population-based cohort of older adults with data collection 2008-2010. Polypharmacy was defined as ≥5 drugs and hyperpolypharmacy as ≥10 drugs. Drugs without relevant propensity of causing adverse drug reactions or drug-drug interactions were not counted. Confounding by indication was addressed by model adjustment for a propensity score for polypharmacy.
The median age of study participants was 70 years, 10.7% had multi-morbidity, and 47.4% took five drugs or more (8.6% took ≥10 drugs). During 4.4 years of follow-up, 87 participants died of a cause other than cancer. Statistically significant, more than twofold increased non-cancer mortality was observed for subjects with polypharmacy or hyperpolypharmacy in a model adjusted for age, sex, education, lifestyle variables, and comorbidity, but associations lost statistical significance after additional adjustment for a propensity score for polypharmacy. However, a significant interaction of hyperpolypharmacy and multi-morbidity was detected (p = 0.019). The hazard ratio for the association of hyperpolypharmacy with non-cancer mortality was 1.42 (95%CI 0.57; 3.57) in subjects without multi-morbidity and 0.51 (95%CI 0.11; 2.27) in subjects with multi-morbidity.
Polypharmacy was not independently associated with non-cancer mortality. This study highlights the importance to adjust for confounding by indication in studies on polypharmacy by a propensity score. The detected interaction suggests that hyperpolypharmacy can be indicated in subjects with multi-morbidity and may only be harmful in subjects without multi-morbidity.
本研究旨在调查多重用药与非癌症死亡率之间的关联是否独立于共病，以及是否并非由适应证混杂所致。
对2687名德国基于人群的老年队列参与者进行分析，数据收集于2008年至2010年。多重用药定义为服用≥5种药物，超多重用药定义为服用≥10种药物。无相关引起药物不良反应或药物相互作用倾向的药物不计入。通过对多重用药倾向评分进行模型调整来处理适应证混杂问题。
研究参与者的中位年龄为70岁，10.7%患有多种疾病，47.4%服用五种或更多药物（8.6%服用≥10种药物）。在4.4年的随访期间，87名参与者死于非癌症原因。在对年龄、性别、教育程度、生活方式变量和共病进行调整的模型中，观察到多重用药或超多重用药的受试者非癌症死亡率有统计学意义的、超过两倍的增加，但在对多重用药倾向评分进行额外调整后，这种关联失去了统计学意义。然而，检测到超多重用药与多种疾病之间存在显著交互作用（p = 0.019）。在无多种疾病的受试者中，超多重用药与非癌症死亡率关联的风险比为1.42（95%CI 0.57；3.57），在有多种疾病的受试者中为0.51（95%CI 0.11；2.27）。
多重用药与非癌症死亡率并非独立相关。本研究强调了在多重用药研究中通过倾向评分调整适应证混杂的重要性。检测到的交互作用表明，超多重用药在患有多种疾病的受试者中可能有意义，而在无多种疾病的受试者中可能有害。
