Door-to-GDMT time: The effect of de novo diagnosis of heart failure on guideline-directed medical therapy optimisation during the rapid-up titration programme and on prognosis

Introduction

Early initiation of guideline (GL)-directed medical therapy (GDMT) has been shown to have a significant prognosis-modifying effect according to the heart failure (HF) landmark trials. Moreover, the 2023 ESC HF GLs recommend the rapid up-titration (RT) of GDMT after a HF hospitalisation (HFH) for all non-fully-therapy-optimised HF patients within 6 weeks, in light of the STRONG-HF trial.

Aims

To assess the application of GDMT after a 6-week RT programme (RTP) among de novo and non-de novo HF patients and to evaluate the prognostic (all-cause mortality [ACM], HFH) differences among these subgroups.

Patients and methods: In accordance with the 2023 ESC HF GLs, a 6-week RTP was designed and implemented in the daily clinical practice of HF Outpatient Clinics of five national secondary/tertiary cardiology centres. The data of a consecutive group of the first 146 patients (male: 79%, age: 56 [49-65] years, de novo HF: 68%, LVEF: 23 [20-30]%, NT-proBNP at discharge: 1397 [746-3066] pg/mL, GDMT at discharge: RASi/target doses [TD] of RASi: 100%/16%, βB/TD βB: 97%/6%, MRA/TD MRA: 99%/77%, SGLT2i: 97%, triple therapy [TT: RASi + βB + MRA]/TD TT: 98%/1%, quadruple therapy [QT: TT + SGLT2i]/TD QT: 95%/1%) involved in RTP after an HFH, and completing the RTP were assessed in the current analysis. The composite endpoint of ACM/HFH was investigated using Kaplan-Meier analysis and the log-rank test, while the independent predictors of ACM/HFH were evaluated using Cox regression analysis.

Results

After the 6-week RTP, the ratio of the implementation of GDMT with TDs improved remarkably (≥50% of TDs of QT: 75%; TD QT: 47%). De novo HF patients were more likely to receive TDs of QT (53% vs. 33%, p=0.032; de novo vs. non-de novo patients, respectively) at the end of RTP. After the median follow-up period (FUP) of 388 [237-531] days, the composite of ACM/HFH affected the de novo HF subgroup less frequently (3% vs 17%, p=0.007; de novo vs. non-de novo patients, respectively). The negative independent predictors of the composite outcome of ACM/HFH were de novo diagnosis of HF (HR: 0.085, 95% CI: 0.012-0.615, p=0.015) and male gender (HR: 0.130, 95% CI: 0.023-0.747, p=0.022). In contrast, diabetes (HR: 9,287, 95% CI: 1.489-57.912, p=0.017) and pre-discharge NT-proBNP (/10 pg/mL increase: HR: 1.024, 95% CI: 1.001-1.048, p=0.040) influenced the risk of the composite endpoint of ACM/HFH positively.

Conclusions

Based on our retrospective multicentre study, the accomplishment of RTP in HF could be conducted successfully in real-world clinical setting as well, resulting in a high proportion of patients receiving TDs of GDMT. Moreover, as a consequence of the GDMT RTP, de novo HF diagnosis was associated with more favourable treatment and better prognosis even within a short FUP, raising the importance of the early implementation and RT of GDMT.