Underuse of heart failure medications and poor long-term prognosis in chronic heart failure patients with polypharmacy – A report from the CHART-2 study

Background: In patients with chronic heart failure (CHF), comorbidities are often managed with multiple medications, characterized by polypharmacy, leading to increased risk of potentially inappropriate medication and adverse effects. Methods: We studied 4,876 consecutive patients with CHF (Stage C/D, age 69.0 ± 12.3 years) in the CHART-2 study to evaluate the association among polypharmacy, underuse of HF medications, and all-cause death. Polypharmacy was defined as the daily use of ≥ 8 medications for the survival classification and regression tree analysis. Results: The average number of medications was 10 in the polypharmacy group and 5 in the non-polypharmacy group, respectively. Over a median of 8.3 (4.1-11.7) years, the incidence rate of all-cause death was significantly higher in the polypharmacy group (n = 2,108) than in the non-polypharmacy group (57.3 % vs. 40.6 %; adjusted hazard ratio [aHR] 1.34 (95 %CI, 1.22-1.48), P < 0.001), even in age < 55 years (26.6 % vs. 14.3 %; adjusted hazard ratio [aHR] 1.61 (95 %CI, 1.04-2.50), P = 0.033). In patients with polypharmacy, those without renin-angiotensin system inhibitors (RAS-I) and/or beta-blockers (N = 1,023) were associated with increased incidence of all-cause death as compared with those with both medications (aHR 1.18; 95 %CI 1.04-1.35, P = 0.012). Conclusions: Polypharmacy was associated with poor long-term prognosis, even in younger patients with CHF. Among 4,876 patients with CHF, 1023 (20.9%) with polypharmacy and underuse of RAS-I and/or beta-blocker were associated with increased risk of all-cause death.