Effect of guideline-directed medical therapy titration following heart failure hospitalisation in patients with heart failure with reduced ejection fraction on long-term mortality
T G Gergely, Z Forrai, P P Schaffer, A Kazay, L F Hanuska, K Czurko, D Pilecky, P Andreka, Z Piroth, F Banfi-Bacsardi, B MukAbstract
Background
Despite the recent advances in the pharmacotherapy of heart failure with reduced ejection fraction (HFrEF), the mortality and morbidity burden of HFrEF is still high. Data from contemporary registries show that the uptake of quadruple therapy (QT: RASi [ACEi/ARB/ARNI] + βB + MRA + SGLT2i) of guideline-directed medical therapy (GDMT) has been slow in recent years, and only a fraction of patients reached target doses (TDs) of QT after hospitalisation for HF.
Aim
To assess the effect of post-hospitalisation GDMT dose titration on long-term mortality in HFrEF patients.
Methods
Data from consecutive patients hospitalised for HFrEF between 2021 and 2024 were retrospectively analysed. Of 420 hospitalised patients, 335 survived at least one year with available data regarding medications (total cohort [TC]). The application of QT was categorized based on the percent of TD achieved (e.g., no QT, doses between 1-49%, 50-99% and 100%). QT dose categories were compared between hospital discharge and one year of follow-up. Patients who were maintained on the same dose category or down-titrated at one year of follow-up were compared to patients who were up-titrated. All-cause mortality was assessed via Kaplan-Meier curves and log-rank test. The independent predictors of mortality were examined by multivariate logistic regression analysis.
Results
Baseline characteristics of the TC at index hospitalisation were: male sex: 77%, age: 60 [51-70] years, NT-proBNP: 5033 [2438-8930] pg/mL, LVEF: 25 [20-30] %, hypertension: 67%, coronary artery disease: 44%, atrial fibrillation: 42%, type 2 diabetes (T2DM): 32%, eGFR < 60 mL/min/1.73m2: 48%. At discharge, QT was implemented in 62% of the cohort, with 52% of patients achieving 1-49%, 8% achieving 50-99% and 2% achieving 100% of the TD, respectively. After one year of follow-up, 56% of patients received QT, with 31% achieving 1-49%, 19% achieving 50-99% and 6% achieving 100% of TD, respectively. 16% of patients were down-titrated at one year of follow-up compared to hospital discharge, 57% were maintained on the same dose, and 27% were up-titrated. Baseline characteristics at index hospitalisation of patients with maintained QT dose or down-titration were similar to up-titrated patients. All-cause mortality was significantly lower in up-titrated patients with a median follow-up of 620 days (p = 0.001, log-rank test). Multivariate regression analysis revealed that QT titration status at one year remained an independent predictor of mortality.
Conclusions
In our real-world cohort of hospitalised HFrEF patients, up-titration of QT during one year of follow-up after a HF hospitalisation was associated with significantly better survival compared to patients maintained on the same dose or down-titrated, despite similar baseline characteristics. In-hospital initiation of QT and up-titration after hospitalisation with optimal adherence to therapy is necessary for better outcomes in HFrEF patients.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.