Real-world evidence of the impact of polypharmacy on mortality and recovery after hip fracture in elderly patients

Polypharmacy is a common problem in older adults with hip fractures and may negatively affect postoperative outcomes. The aim of this study was to evaluate the association between polypharmacy, including severe polypharmacy, and clinical outcomes in older adults admitted to hospital with hip fracture. A real-life observational study was conducted at a tertiary care hospital in Spain, including patients aged ≥ 70 years who underwent hip fracture surgery between January 1, 2017, and December 31, 2018. Data were extracted from electronic medical records, including demographic details, comorbidities, and medication use. Polypharmacy was defined as the use of five or more medications, and severe polypharmacy as the use of ten or more medications. Mortality rates were analyzed at 30 days, 6 months, 1 year, 2 years, and 5 years post-surgery using Kaplan-Meier survival curves and Cox regression analysis. Among 644 patients included (mean age 84.5 years, 70.5% women), 63.8% had polypharmacy and 19.1% had severe polypharmacy. Compared with patients without polypharmacy, those with polypharmacy, regardless of severity, showed higher mortality at 30 days (8.4% and 10.3% vs 3.9%), 6 months (21.3% and 21.4% vs 10.8%), 1 year (26.6% and 33.3% vs 11.6%), 2 years (38.8% and 46.0% vs 14.2%), and 5 years (68.5% and 76.2% vs 26.3%) (all p ≤ 0.05). Crude hazard ratios for 5-year mortality were 3.65 (95% CI 2.73-4.88) for patients taking 5-9 drugs and 4.51 (95% CI 3.26-6.24) for those taking ≥ 10 drugs; after full adjustment, these remained 3.12 and 3.46, respectively. Patients with polypharmacy also had more red blood cell transfusions, major complications, and worse functional recovery. Polypharmacy was associated with worse postoperative morbidity, poorer functional recovery, and higher mortality in older adults with hip fracture. These findings suggest that medication burden may serve as a marker of clinical vulnerability rather than an isolated causal factor. Prospective interventional studies are needed to determine whether medication optimization improves outcomes.