Dose-Response Relationships Between Polypharmacy and All-Cause and Cause-Specific Mortality Among Older People

Although medicines are prescribed based on clinical guidelines and expected to benefit patients, both positive and negative health outcomes have been reported associated with polypharmacy. Mortality is the main outcome, and information on cause-specific mortality is scarce. Hence, we investigated the association between different levels of polypharmacy and all-cause and cause-specific mortality among older adults.

The English Longitudinal Study of Ageing is a nationally representative study of people aged 50+. From 2012/2013, 6 295 individuals were followed up to April 2018 for all-cause and cause-specific mortality. Polypharmacy was defined as taking 5-9 long-term medications daily and heightened polypharmacy as 10+ medications. Cox proportional hazards regression and competing-risks regression were used to examine associations between polypharmacy and all-cause and cause-specific mortality, respectively.

Over a 6-year follow-up period, both polypharmacy (19.3%) and heightened polypharmacy (2.4%) were related to all-cause mortality, with hazard ratios of 1.51 (95% CI: 1.05-2.16) and 2.29 (95% CI: 1.40-3.75) respectively, compared with no medications, independently of demographic factors, serious illnesses and long-term conditions, cognitive function, and depression. Polypharmacy and heightened polypharmacy also showed 2.45 (95% CI: 1.13-5.29) and 3.67 (95% CI: 1.43-9.46) times higher risk of cardiovascular disease deaths, respectively. Cancer mortality was only related to heightened polypharmacy.

Structured medication reviews are currently advised for heightened polypharmacy, but our results suggest that greater attention to polypharmacy in general for older people may reduce adverse effects and improve older adults' health.