Prognostic effect of rapid-up titration programme of guideline-directed medical therapy in heart failure: real-world experience from a multicentre observational study

Introduction

The 2023 ESC Heart Failure (HF) Guidelines (GLs) undoubtedly underscore the strategic role of the rapid up-titration (RT) of GL-directed medical therapy (GDMT) after a HF hospitalisation (HFH) as a consequence of the results of the STRONG-HF trial. Despite the clear recommendation, real-world data on the efficacy and prognostic value of RTP are lacking.

Aims

To assess the impact of a 6-week, universal RTP on prognosis (all-cause mortality [ACM], HFH) in a real-world, consecutive HF patient cohort.

Patients and methods: After the publication of the 2023 ESC HF GLs, a 6-week RTP with weekly visits, guided by the safety indicators of the STRONG-HF trial, was implemented as part of the routine care of HF Outpatient Clinics at 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%) participating in RTP after an index HFH, accomplishing the programme were evaluated in the current retrospective, multicentre analysis. ACM, HFH, and the composite endpoint of ACM/HFH events were assessed as well. The independent predictors of ACM/HFH were evaluated using Cox regression analysis.

Results

After the 6-week RTP, the proportion of patients on TDs of GDMT increased significantly (TD RASi: 73%, TD βB: 58%, TD MRA: 91%, ≥ 50% of TDs of QT: 75%, TD QT: 47%). After a median follow-up period (FUP) of 388 [237-531] days, ACM occurred in 4% of the total cohort; 5% of patients had a rehospitalisation for HF; and the composite endpoint of ACM/HFH occurred in 8% of patients. According to the multivariate Cox-regression analysis, 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) proved to be negative predictors, while 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=0.017) were positive predictors of the composite endpoint of ACM/HFH.

Conclusions

According to our retrospective multicentre observational study, the implementation of the RTP recommended by the ESC 2023 HF Guidelines was feasible in everyday clinical practice. Furthermore, as a result of the RTP, a large proportion of patients receiving TDs of QT at the end of the RTP could be achieved, leading to a favourable prognosis. De novo diagnosis of HF and male gender reduced the risk of the composite endpoint of ACM/HFH, while diabetes and pre-discharge NT-proBNP level proved to be the risk-increasing factors.