NT-proBNP does not influence beneficial effects of high-intensity care in hospitalized acute HF patients
NT-proBNP and high-intensity care for acute heart failure: the STRONG-HF trialLiterature - Adamo M, Pagnesi M, Mebazaa A, et al. - Eur Heart J. 2023 May 22;ehad335 [Online ahead of print]. doi: 10.1093/eurheartj/ehad335
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.
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.
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.
- 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).
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.”