NT-proBNP monitoring does not reduce HF rehospitalizations in HFpEF

In hospitalized HFpEF patients, postdischarge monitoring of NT-proBNP did not lower the primary endpoint of HF rehospitalization at 6 months compared with usual care alone but did result in a lower mortality rate.

This summary is based on the publication of Pascual-Figal DA, Hernández-Vicente A, Pastor-Pérez F, et al. - N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study. Eur J Heart Fail. 2024 Apr 12;26(4):776-784. doi: 10.1002/ejhf.3222

Introduction and methods

Background

The recent STRONG-HF trial demonstrated that after hospital admission for acute HF, a high-intensity care strategy of rapid uptitration of guideline-directed medical therapies (GDMTs) initiated before discharge and close follow-up—including monitoring of natriuretic peptide (NP) levels—was associated with a higher proportion of patients uptitrated to full GDMT doses and improved clinical outcomes [1,2]. However, patients with HFpEF represented only 15% of the study population. Moreover, there are no studies that have specifically addressed the impact of NP monitoring on HFpEF management during the vulnerable phase after discharge.

Aim of the study

The study aim was to assess the clinical benefit of incorporating NT-proBNP monitoring into the postdischarge management of HFpEF patients.

Methods

The NICE study was a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study in which 157 hospitalized patients with HFpEF (LVEF >50%), NYHA class III–IV HF symptoms, elevated NT-proBNP levels, and diastolic dysfunction who were treated with intravenous furosemide ≥40 mg were included from 2016 through 2019. At the time of discharge, study participants were randomized to either NT-proBNP monitoring plus usual care or usual care alone. All patients had the same clinical follow-up visits at 2, 4, and 12 weeks. For patients allocated to NT-proBNP monitoring, the investigators had access to NT-proBNP measurements obtained at the follow-up visits, which they used to adjust GDMTs according to clinical criteria, with no specific indications in the study protocol.

The study was terminated before reaching the target sample size (n=420) because of COVID-related restrictions and based on anticipated futility for the primary endpoint in the first intermediate analysis.

Outcomes

The primary endpoint was the incidence of rehospitalization for HF at 6 months, defined as unplanned hospital admission for ≥24 hours due to HF decompensation. Secondary endpoints were: (1) worsening HF events; (2) change in quality of life at 3 and 6 months, as evaluated with the KCCQ and Minnesota Living with Heart Failure Questionnaire; (3) change in 6-minute walk distance (6MWD) at 6 months; (4) mortality (including all-cause mortality and CV death); (5) hospitalization for any reason; and (6) any adverse event, defined as any worsening HF event, hospitalization for any reason, or death.

The exploratory endpoint was changes in GDMT doses across visits.

Main results

• The primary endpoint of HF rehospitalization occurred in 10 patients (12.8%) randomized to NT-proBNP monitoring and 9 patients (11.4%) in the control group (HR: 1.15; 95%CI: 0.47–2.81; P=0.760).
• The mortality rate was lower in the NT-proBNP monitoring group compared with the control group (1.3% vs. 10.1%; HR: 0.12, 95%CI: 0.02–0.09; P=0.048). The cause of death was refractory HF in the only deceased patient in the NT-proBNP monitoring group and in 5 of the 8 patients in the control group.
• The other secondary endpoints did not show a significant difference between the NT-proBNP monitoring and control groups. The HR was 0.89 (95%CI: 0.44–1.82; P=0.752) for any worsening HF-related event, 0.64 (95%CI: 0.29–1.41; P=0.265) for non–HF-related hospitalization, and 0.68 (95%CI: 0.39–1.18; P=0.171) for any adverse clinical event.
• In both study groups, the quality of life and 6MWD improved from baseline to 6 months (all P≤0.040), but there was no significant difference between the groups (all P>0.05).
• At 6 months, patients in the NT-proBNP monitoring group received higher doses of furosemide and RAASi (ACEi/ARB) compared with the control group (both P≤0.006), while beta-blocker and MRA doses were similar (both P>0.05).

Conclusion

In this multicenter PROBE study among 157 hospitalized patients with HFpEF, postdischarge monitoring of NT-proBNP levels, in addition to usual care, did not reduce the incidence of the primary endpoint of HF rehospitalization at 6 months compared with usual care alone. However, the mortality rate was lower in the NT-proBNP monitoring group. These patients also received higher diuretic and RAASi doses at 6 months, as investigators adjusted GDMT doses in this study arm based on the NT-proBNP measurements at the clinical follow-up visits.

The authors believe their findings, combined with the STRONG-HF trial results, “imply that it is not solely about guiding therapy based on NT-proBNP levels but rather about integrating NT-proBNP information to enhance comprehensive clinical decision-making in a complex condition like HFpEF.”

Find this article online at Eur J Heart Fail.

References

1. Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): A multinational, open-label, randomised, trial. Lancet 2022;400:1938–1952. https://doi.org/10.1016/S0140-6736(22)02076-1
2. Adamo M, Pagnesi M, Mebazaa A, Davison B, Edwards C, Tomasoni D, et al. NT-proBNP and high intensity care for acute heart failure: The STRONG-HF trial. Eur Heart J 2023;44:2947–2962. https://doi.org/10.1093/eurheartj/ehad335