The importance of continuous up-titration and long-term application of guideline-directed medical therapy on prognosis after hospitalisation for heart failure
TL;DR
The long-term use and the achieved doses of QT after a hospitalisation for HF (HFH) in a consecutive cohort of HFrEF patients was analyzed and the effect of the achieved doses on prognosis (all-cause mortality [ACM], HFH, composite of ACM/HFH) was evaluated.
Abstract
The 2021 ESC Heart Failure (HF) Guidelines (GLs) and their 2023 Focused Update clearly recommend the early implementation and up-titration of quadruple therapy (QT: RASi + βB + MRA + SGLT2i) to target doses (TDs) in patients with HF with reduced ejection fraction (HFrEF), emphasising the prognostic role of “time-to-GDMT”. Despite the strong recommendations in the recent international HF Guidelines, the TDs achieved in daily clinical practice are significantly lower than those recommended in the GLs. To analyse the long-term use and the achieved doses of QT after a hospitalisation for HF (HFH) in a consecutive cohort of HFrEF patients; and to evaluate the effect of the achieved doses on prognosis (all-cause mortality [ACM], HFH, composite of ACM/HFH). Patients and methods: We retrospectively evaluated the data of a consecutive HFrEF patient cohort hospitalised for HF between 2021 and 2025 (n=551, male: 75%, age: 63 [52-71] years, de novo HF: 42%, LVEF: 25 [20-30]%, coronary artery disease: 45%, hypertension: 68%, diabetes: 40%, eGFR < 60 mL/min/1.73m2: 52%, NT-proBNP at hospital admission: 5866 [2728-10616] pg/mL, GDMT at discharge: RASi/TD RASi: 94%/18%, βB/TD βB: 85%/7%, MRA/TD MRA: 95%/64%, SGLT2i: 68%, triple therapy [TT: RASi + βB + MRA]/TD TT: 82%/2%, QT /TD QT: 61%/2%). QT and its achieved TDs (not on QT vs 1-49% of TD QT vs 50-100% of TD QT) at 1-year follow-up were investigated. ACM, HFH and the composite of ACM/HFH were analysed, and the independent predictors of the composite of ACM/HFH were examined by Cox-regression analysis. At 1 year, the use of GDMT was as follows: RASi/TD RASi: 89%/34%, βB/TD βB: 85%/22%, MRA/TD MRA: 89%/55%, SGLT2i: 69%, TT/TD TT: 76%/9%, QT/TD QT: 60%/7%. At 1 year, 40% of the total cohort (TC) were not on QT, 31% of TC had 1-49% TD QT, while 29% of the TC were on 50-100% TD QT. During the median 670 [335-1085] days of follow-up, ACM affected 25% of the TC, while 25% of TC were re-hospitalised for HF, and the composite endpoint of ACM/HFH was observed in 39% of TC. Higher doses of QT were associated with a more favourable prognosis (ACM: 3% vs 7% vs 21%, p<0.001; ACM/HFH: 18% vs 24% vs 38%, p=0.005; not on QT vs 1-49% TD QT vs 50-100% TD QT, respectively). According to the multivariate Cox-regression analysis, the application of CRT (HR: 2.089, 95% CI: 1.041-4.191, p=0.038) and NT-proBNP (/100 pg/mL, HR: 1.006, 95% CI: 1.001-1.012, p=0.032) at discharge proved to be positive-, while ≥50% of TD QT use at 1 year (HR: 0.452, 95% CI: 0.212-0.964, p=0.040) was a negative predictor of ACM/AHF. Dose-dependent, long-term QT use remarkably influenced the risk of ACM and the composite endpoint of ACM/HFH in a consecutive HFrEF patient population after an HFH. ≥50% of TD QT use at 1 year reduced the risk of ACM/HFH by 55%, highlighting the need for continuous efforts to optimise doses of GDMT and to maintain long-term the prognosis-modifying pharmacotherapy.File 1