Association of Polypharmacy with Survival, Complications, and Healthcare Resource Use after Elective Noncardiac Surgery

BACKGROUND: Polypharmacy is increasingly prevalent in older patients and is associated with adverse events among medical patients. The impact of polypharmacy on outcomes after elective surgery is poorly described. The authors' objective was to measure the association of polypharmacy with survival, complications, and resource use among older patients undergoing elective surgery. METHODS: After registration (NCT03133182), the authors identified all individuals older than 65 yr old having their first elective noncardiac surgery in Ontario, Canada, between 2002 and 2014. Using linked administrative data, the authors identified all prescriptions dispensed in the 90 days before surgery and classified people receiving five or more unique medications with polypharmacy. The associations of polypharmacy with 90-day survival (primary outcome), complications, length of stay, costs, discharge location, and readmissions were estimated after multilevel, multivariable adjustment for demographics, comorbidities, previous healthcare use, and surgical factors. Prespecified and post hoc sensitivity analyses were also performed. RESULTS: Of 266,499 patients identified, 146,026 (54.8%) had polypharmacy. Death within 90 days occurred in 4,356 (3.0%) patients with polypharmacy and 1,919 (1.6%) without (adjusted hazard ratio = 1.21; 95% CI, 1.14 to 1.27). Sensitivity analyses demonstrated no increase in effect when only high-risk medications were considered and attenuation of the effect when only prescriptions filled in the 30 preoperative days were considered (hazard ratio = 1.07). Associations were attenuated or not significant in patients with frailty and higher comorbidity scores. CONCLUSIONS: Older patients with polypharmacy represent a high-risk stratum of the perioperative population. However, the authors' findings call into question the causality and generalizability of the polypharmacy-adverse outcome association that is well documented in nonsurgical patients.