Multi-trajectories of polypharmacy composition and clinical outcomes by frailty status: a longitudinal cohort study

Background While polypharmacy is prevalent among older adults, the impact of different medication composition patterns on clinical outcomes and how these associations vary by frailty status remains unclear. We aimed to identify distinct longitudinal patterns of polypharmacy composition and clinical outcomes, stratified by frailty status, in older adults. Methods From Taiwan’s National Health Insurance research database, a group-based multi-trajectory modelling was adopted to identify distinct longitudinal patterns of polypharmacy composition among older adults with polypharmacy. Cox proportional hazards models were used to assess the association between polypharmacy patterns and subsequent 6-year risk of all-cause mortality, all-cause hospitalisation, unplanned hospitalisation and fracture-specific hospitalisation. Findings Among 787 072 older adults (mean [SD] age, 76.2 [7.0] years; 361,767 [46.0%] male), we identified three distinct polypharmacy composition patterns: cardiometabolic medications dominant (44·2%; mean of 5.6 cardiometabolic versus 0.9 symptomatic treatment and 0.3 psychotropic medications), symptomatic treatment medications dominant (25·6%; mean of 1.9 cardiometabolic versus 3.2 symptomatic treatment and 1.2 psychotropic medications), and cardiometabolic and symptomatic treatment medications dominant (30·2%; mean of 5.6 cardiometabolic versus 3.4 symptomatic treatment and 1.0 psychotropic medications). These medication patterns remained stable throughout the 2-year trajectory period across all groups. Compared to the cardiometabolic medications dominant group, the symptomatic treatment medications dominant group and the cardiometabolic and symptomatic treatment dominant groups had higher risks of all-cause mortality (adjusted HR 1·22 [95% CI 1·21–1·23] and 1·16 [1·15–1·18]), all-cause hospitalisation (1·09 [1·09–1·10] and1·08 [1·07–1·09]), unplanned hospitalisation (1·07 [1·06–1·08] and 1·08 [1·07–1·09]), and fracture-specific hospitalisation (1·20 [1·18–1·22] and 1·09 [1·07–1·11]). Risk differences attenuated with increasing frailty, except for fracture-specific hospitalisation. Interpretation Symptomatic treatment medications dominant patterns were associated with higher risks of adverse outcomes, with these associations generally attenuating with increasing frailty severity, except for fracture risk.