Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial...

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.