The effect of increase in NT-proBNP on the efficacy and safety of a rapid up-titration of guideline-directed medical therapy in patients with low predischarge NT-proBNP

Introduction

The 2023 Focused Update of the 2021 ESC Heart Failure (HF) Guidelines strongly recommend the rapid up-titration (RT) of guideline-directed medical therapy (GDMT) in all patients after heart failure hospitalization. In the STRONG-HF trial, which forms the basis of this recommendation, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was one of the parameters used as a safety indicator to assess treatment safety; if NT-proBNP increased >10% compared to predischarge levels, beta-blocker (BB) up-titration was not recommended. A predischarge NT-proBNP>1500 pg/ml was one of the inclusion criteria of the study. We have limited information about RT in patients with predischarge NT-proBNP<1500 pg/ml.

Aims

The aim of our study was to evaluate the safety and efficacy of RT in patients with predischarge NT-proBNP<1500 pg/ml and titrated BB despite an NT-proBNP increase exceeding 10%.

Patients and Methods: According to the 2023 Focused Update of the 2021 ESC HF Guidelines a 6-week RT protocol was implemented in routine practice across the HF Outpatient Clinics of five secondary/tertiary cardiology centers in Hungary. NT-proBNP was measured routinely at discharge from the hospital and 2 times during RT (Week 2 and Week 4). From the first 146 patients (age: 56 [49-65] years, male: 79%, de novo HF: 68%, LVEF: 23 [20-30]%, NT-proBNP predischarge: 1397 [746-3066] pg/mL) completing the RT programme we identified patients who underwent BB up-titration despite an NT-proBNP increase >10% at Week 2 and/or Week 4 and had a predischarge NT-proBNP <1500 pg/ml (Group 1, n=26, age: 54 [48-66] years, male: 85%, de novo HF: 69%, LVEF: 24 [20-31]%, NT-proBNP predischarge: 729 [345-1005] pg/mL). The control group included patients with no or <10% NT-proBNP elevation at Week 2 and/or Week 4 (Group 2, n=74, age: 56 [48-62] years, male: 79%, de novo HF: 72%, LVEF: 22 [18-26]%, NT-proBNP predischarge: 1700 [981-3446] pg/mL).

Results

No significant differences were observed between the two groups regarding RT success (Group 1 vs Group 2: BB target dose (TD) 84.6% vs 62.1%, p=0.050; RAASi TD: 80.8% vs 75.7%, p=0.595; MRA TD: 88.5% vs 93.2%, p=0.425; SGLT2i: 96.2% vs 97.3%, p=0.769; triple therapy (TT) TD: 69.2% vs 50.0%, p=0.090; quadruple therapy (QT) TD: 69.2% vs 47.3%, p=0.054). Similarly, no significant difference was observed between the two groups in terms of 6-week cardiovascular (CV) hospitalization and mortality (no events in Group 1 vs 1 CV hospitalization in Group 2).

Conclusion

In a subgroup of patients with predischarge NT-proBNP<1500 pg/ml, that was excluded from STRONG-HF trial, up-titration of BB in patients with >10% increment of NT-proBNP during RT programme seems to be safe and effective in terms of GDMT optimization.