Multitrajectories of polypharmacy composition patterns and their impacts on clinical outcomes among older people: a longitudinal cohort study

Background: While the associations between polypharmacy (i.e., concomitant use of five and more drugs) and adverse outcomes among older people has been extensively discussed, whether these association derived from the “number” or “composition” of these concomitantly used drugs remains unanswered.

Objectives: This population-based cohort study aims to assess whether different compositions of medications have different impacts on adverse outcomes among older people who received polypharmacy.

Methods: Using Taiwan's National Health Insurance database, this study identified beneficiaries aged 65 years or older who received polypharmacy (defined as concomitant use of five or more medications within a one-year inclusion period) as eligible study subjects. Time-varying variables were set to quarterly capture four categories (cardiometabolic, psychotropic, symptom relief, and other drugs) of drugs used by the study subjects over a 2-year trajectory period. Utilizing the group-based multitrajectory modeling, distinct subtypes of trajectories in composition of polypharmacy across the four categories of drugs were identified. Cox proportional hazards models were employed to investigate the association between the identified subtypes in composition of polypharmacy and adverse outcomes (all-cause hospitalization, fracture-specific hospitalization, and all-cause mortality) during the follow-up.

Results: Among 50,000 eligible participants, we identified three subtypes in composition of polypharmacy: cardiometabolic medication-dominant (46.2%), symptom relief medication-dominant (25.0%), and extensive use of cardiometabolic and symptom relief medications (28.8%). In comparison with the cardiometabolic medication-dominant group, the symptom relief medication-dominant group manifested significantly elevated risks of all-cause mortality [adjusted hazard ratio (aHR) 1.20, 95% confidence interval (CI) 1.16-1.24], all-cause hospitalization [aHR 1.09, 95% CI 1.06-1.12], and fracture-specific hospitalization [aHR 1.24, 95% CI 1.14-1.34].

Conclusions: While all fall within the definition of polypharmacy, polypharmacy featured predominantly by the use of symptom relief drugs carries an elevated risk of mortality and hospitalization as compared with that featured as cardiometabolic-dominant. A comprehensive understanding of drug composition in polypharmacy is crucial for risk stratification and effective care to elderly adults.