Real-life implementation of guideline-recommended medical therapy in heart failure with reduced ejection fraction: Effects on prognosis and left ventricular ejection fraction. Primary results of TITRATE-HF

Aims: Guideline-recommended medical therapy (GRMT) improves outcomes in heart failure (HF) with reduced ejection fraction (HFrEF), yet implementation remains suboptimal. TITRATE-HF prospectively evaluated GRMT implementation across different HFrEF stages, and its effect on 1-year prognosis and left ventricular ejection fraction (LVEF). Methods and results: TITRATE-HF is an observational cohort study across 48 hospitals in the Netherlands (June 2022–February 2024). A total of 4288 patients were enrolled. This primary analysis includes 12-month follow-up data of all HFrEF patients (n = 3367), stratified into de novo, chronic, and worsening HF. Longitudinal trends in GRMT prescription rates and dosages were analysed. Serial echocardiographic data assessed changes in LVEF between baseline and 12 months. Kaplan–Meier analysis assessed the composite endpoint of all-cause death or HF hospitalization. Median age was 71 years (interquartile range [IQR] 63–78), 29% were female, and 56% had non-ischaemic cardiomyopathy. In de novo HFrEF (n = 1353), quadruple therapy was 47.2% at 6 weeks, 64.7% at 3 months, 69.5% at 6 months, and 64.4% at 12 months. In chronic/worsening HFrEF (n = 1625), quadruple therapy increased from 44.6% at baseline to 54.6% at 12 months, primarily driven by greater sodium–glucose co-transporter 2 inhibitor uptake (66.0% to 78.5%). Among de novo HFrEF patients with serial echocardiograms (n = 752), median LVEF improved by 10% (IQR 3–17%) in ischaemic versus 15% (IQR 9–24%) in non-ischaemic cardiomyopathy (p < 0.001). Early quadruple GRMT initiation (within 6 weeks) and higher 6-month doses were associated with greater LVEF improvement. At 12 months, the composite endpoint occurred in 13.3%, 13.3%, and 43.8% of de novo, chronic, and worsening HFrEF patients, respectively. Conclusions: These findings highlight the importance of early and intensive GRMT implementation, and emphasize the need for continuous dose titration beyond the initial phase to improve LVEF and clinical outcomes.