Ben Schöttker1,2,3, Kai-Uwe Saum4, Dana Clarissa Muhlack4,5, Liesa Katharina Hoppe4,5, Bernd Holleczek6, Hermann Brenner4,5. 1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. b.schoettker@dkfz-heidelberg.de. 2. Network Aging Research, University of Heidelberg, Heidelberg, Germany. b.schoettker@dkfz-heidelberg.de. 3. Institute of Health Care and Social Sciences, FOM University, Essen, Germany. b.schoettker@dkfz-heidelberg.de. 4. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. 5. Network Aging Research, University of Heidelberg, Heidelberg, Germany. 6. Saarland Cancer Registry, Saarbrücken, Germany.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
Death; Drug related; Epidemiology; Multi-morbidities
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