High-dose guideline-directed medical therapy at discharge reduces mortality in hospitalized patients with heart failure with reduced ejection fraction: evidence from the HEROES study

Abstract Introduction Guideline-directed medical therapy (GDMT) is recommended in patients with heart failure and reduced ejection fraction (HFrEF) to reduce hospitalizations and mortality. Every medical contact, including hospitalization, should be used to initiate or up-titrate GDMT. However, still only a few patients receive high-dose GDMT. Purpose To identify the relationship between the discharge intensity of GDMT and mortality in hospitalized patients with HFrEF. Methods The analysis was conducted in a group of 464 patients (84 women and 380 men) hospitalized due to HFrEF, selected from among the 1422 participants of the HEROES study—a prospective, multicenter, observational study including patients with HF recruited at 41 polish centers and endorsed by the Polish Cardiac Society. For the purpose of this analysis, the patients were divided into two groups: 1/ hdGDMT + - patients treated with high-dose GDMT, defined as the administration of all four GDMT classes at doses ≥50%, and 2/ hdGDMT - - patients treated with lower doses of GDMT. To estimate the survival curves for these two groups, Kaplan–Meier analysis was used. To adjust the effect of high-dose GDMT for other risk factors of mortality, a multivariable analysis was performed using the Cox proportional hazards model. Results The mean (±SD) age of the study group was 64. 2 ± 14. 0 years, and the mean left ventricular ejection fraction (LVEF) was 26. 3 ± 8. 1%. A total of 178 patients (38. 4%) were hospitalized due to acute heart failure decompensation, and de novo heart failure was diagnosed in 81 patients (17. 5%). One hundred and two patients were discharged on high-dose GDMT. During the follow-up period (118–805 days, median 483 days), death occurred in 94 subjects (20. 3%), significantly more frequently in the hdGDMT – group than in the hdGDMT + group (83 22. 9% vs. 11 10. 8%; log-rank test, p = 0. 0041; Figure 1). In the multivariable Cox model, high-dose GDMT was associated with a significantly lower risk of mortality (hazard ratio HR = 0. 473, 95% confidence interval CI: 0. 242–0. 926, p = 0. 038). Other variables significantly associated with mortality risk included age (HR = 1. 029, 95% CI: 1. 010–1. 049, p = 0. 003), New York Heart Association (NYHA) class (HR = 1. 019, 95% CI: 1. 012–1. 027, p 0. 001), sodium level (HR = 0. 910, 95% CI: 0. 866–0. 956, p = 0. 002), and anemia (HR = 1. 869, 95% CI: 1. 118–3. 124, p = 0. 017). Other factors, such as a history of heart failure, chronic kidney disease, atrial fibrillation, diabetes, and ischemic etiology, did not show statistically significant associations with mortality in the adjusted model. Conclusions Among patients hospitalized for HFrEF who participated in the HEROES study, high-dose GDMT was significantly associated with a reduced risk of mortality, even after adjusting for multiple confounders. These findings support the potential benefit of this treatment strategy and underscore the need for effective uptitration of GDMT. Kaplan-Meier survival curves - 2 groups