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Be part of the knowledge.™NT-proBNP does not influence beneficial effects of high-intensity care in hospitalized acute HF patients
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Background
The recently conducted STRONG-HF trial showed that a high-intensity care (HIC) strategy, consisting of rapid uptitration of guideline-recommended medical therapy (GRMT) and close follow-up, was associated with better outcomes after hospital admission for acute HF (AHF) compared with usual care [1-3]. In the prespecified subgroup analysis, there was a trend towards a larger benefit of HIC over usual care in patients with NT-proBNP levels above the median, although there was no significant interaction [1 ].
Aim of the study
Using data from the STRONG-HF trial, the authors examined the relation of baseline NT-proBNP levels with the efficacy of HIC versus usual care in hospitalized AHF patients and the prognostic significance of changes in NT-proBNP levels during follow-up in the HIC group.
Methods
The STRONG-HF (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) trial was a multicenter, open-label RCT in which 1078 patients hospitalized for AHF were enrolled who showed high NT-proBNP levels (>2500 pg/mL) at screening and a >10% decrease between screening and randomization (with NT-proBNP >1500 pg/mL before discharge). Within 2 days before the anticipated discharge date, participants were randomized to HIC or usual care.
Patients in the HIC group had follow-up visits at 1, 2, 3, and 6 weeks after randomization. In this group, oral doses of ACEi/ARB/ARNI, beta-blocker, and MRA were rapidly uptitrated to full optimal doses at week 2 if measures, including an NT-proBNP change, indicated it was safe to do so. In patients with an NT-proBNP increase >10% relative to the predischarge level, physicians were advised to consider increasing loop diuretic doses and not uptitrating beta-blockers. Baseline NT-proBNP concentrations were available for 1077 patients and follow-up data for 1007.
Outcomes
The primary endpoint was a composite outcome of all-cause mortality or first HF rehospitalization at 180 days. Secondary endpoints included, among others, all-cause mortality at 180 days.
Main results
Baseline NT-proBNP
- Baseline NT-proBNP levels did not influence the beneficial effects of HIC (n=542) versus usual care (n=535) on the primary endpoint, both when patients were divided based on NT-proBNP tertiles (P for interaction=0.1965) and when NT-proBNP level was evaluated as a continuous variable (P for interaction=0.3204).
- Similar results were found for the secondary endpoint (P for treatment-by-tertile interaction=0.5673).
Change in NT-proBNP during follow-up
- From randomization to 1 week after discharge, the NT-proBNP level in the HIC group decreased ≥30% in 149 patients (30%), was stable values (<30% decrease to ≤10% increase) in 212 (43%), and increased >10% in 135 patients (27%).
- At 2 weeks after randomization, patients who had increased NT-proBNP levels at 1 week were less likely to receive >50% target doses of RAASi, beta-blocker, and MRA—SGLT2 inhibitors were not included in the study design—and were on higher doses of loop diuretics compared with patients with stable or decreased NT-proBNP levels (all P<0.0001). After the first weeks postdischarge, these differences became smaller.
- Initially, the rate of all-cause mortality or HF rehospitalization differed between patients with increased, stable, and decreased NT-proBNP levels at 1 week. At 60 days, the rate was 8.3% in patients with a 1-week NT-proBNP increase versus 2.2% in those with a 1-week NT-proBNP decrease (P=0.039), and it was 11.1% and 4.0%, respectively, at 90 days (P=0.045).
- However, the occurrence of all-cause mortality or HF rehospitalization at 180 days (i.e., primary endpoint) was similar (1-week NT-proBNP increase vs. decrease: 13.5% vs. 13.2%; HR: 1.10; 95%CI: 0.51–2.38; P=0.93).
- The rate of 180-day all-cause mortality (i.e., secondary endpoint) was also similar for patients with increased, stable and decreased NT-proBNP (HR for 1-week NT-proBNP increase vs. decrease: 0.43; 95%CI: 0.11–1.59).
Conclusion
In this analysis of the STRONG-HF trial, HIC reduced the rate of all-cause mortality or HF rehospitalization at 180 days (i.e., primary endpoint) in AHF patients compared with usual care, regardless of baseline NT-proBNP levels. In the HIC group, patients who showed increased NT-proBNP levels between randomization and 1 week thereafter were less likely to receive >50% GRMT target doses and were on higher loop diuretic doses compared with those with an NT-proBNP decrease. The early postdischarge NT-proBNP change was associated with a poorer outcome up at 60 and 90 days but not at 180 days.
The authors state the following: “Our analysis suggest[s] a new role for NT-proBNP measurements in the context of rapid uptitration of GRMT as they can alert the physician that the patient has persistent congestion and is not tolerating rapid GRMT uptitration [well], so that beta-blocker titration must be slowed or interrupted and/or higher diuretic doses must be administered.”
References
1. Kimmoun A, Cotter G, Davison B, Takagi K, Addad F, Celutkiene J, et al. Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP and GDF-15, of Heart Failure therapies (STRONG-HF): rationale and design for a multicentre, randomized, parallel-group study. Eur J Heart Fail 2019;21:1459–1467. https://doi.org/10.1002/ejhf.1575
2. Cotter G, Davison B, Metra M, Sliwa K, Voors AA, Addad F, et al. Amended STRONG-HF study design. Eur J Heart Fail 2021;23:1981–1982. https://doi.org/10.1002/ejhf.2348
3. 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
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