Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Patients ≥75 With Atrial Fibrillation

BACKGROUND: Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. METHODS AND RESULTS: We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007–2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD‐9‐CM] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [HR], 1.16; 95% CI, 1.12–1.20) and heart failure (HR, 1.33; 95% CI, 1.29–1.36) but not ischemic stroke (HR, 0.96; 95% CI, 0.92–1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy (HR, 0.87; 95% CI, 0.76–0.99) than among those with polypharmacy (HR, 0.98; 95% CI, 0.91–1.07; P=0.02 for interaction). CONCLUSION: Polypharmacy is common among patients ≥75 with AF, is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ≥75 may lead to improved outcomes.