Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies - STRONG-HF

Contribution To Literature:

The STRONG-HF trial showed that, among patients with admission for acute HF, an intensive treatment strategy of rapid up-titration of guideline-directed medication and close follow-up reduced the risk of 180-day all-cause death or HF readmission compared to usual care.


The goal of the trial was to compare a high-intensity intervention involving up-titration of heart failure (HF) treatments versus usual care among participants with admission for acute HF.

Study Design

The STRONG-HF trial was a multinational, open-label, randomized, parallel-group trial of participants admitted with acute heart failure not on full doses of HF guideline-directed medical therapy (GDMT). Patients were randomized in a 1:1 fashion to high-intensity up-titration (n = 542) or usual care (n = 536). Participants were stratified by left ventricular ejection fraction (LVEF) (≤40% vs. >40%).

High-intensity care involved up-titration of treatments to 100% of recommended doses within 2 weeks of discharge for beta-blockers, angiotensin converting enzyme (ACE) inhibitors (or angiotensin receptor blockers [ARBs] if the patient was intolerant to ACE inhibitors) or angiotensin receptor-neprilysin inhibitors, and mineralocorticoid receptor antagonists, and four scheduled outpatient visits over the 2 months after discharge with monitoring of clinical status, N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, and lab values.

The study was stopped early per Data and Safety Monitoring Board recommendation because of greater than expected between-group differences.

  • Total patients screened: 1,641
  • Total randomized participants: 1,078
  • Study terminated on September 23, 2022
  • Mean patient age: 63 years
  • Percentage female: 39%
  • Percentage Black: 21%

Inclusion criteria:

  • Age 18-85 years
  • Admission within 72 hours before screening for acute HF
  • Hemodynamically stable
  • NT-proBNP >2500 pg/mL and >10% decrease between screening and before randomization (but still >1500 pg/mL)
  • Without treatment of optimal doses of oral HF therapies within 2 days before hospital discharge

Exclusion criteria:

  • Intolerance to beta-blockers, ACE inhibitors, or ARBs

Other salient features/characteristics:

  • 29% with acute coronary syndrome
  • 29% with diabetes
  • 22% with New York Heart Association (NYHA) class IV HF 1 month before hospital admission
  • 15% with LVEF ≥50%
  • Baseline LVEF: 36%
  • Cardiac resynchronization therapy (CRT) at baseline: 1%

Principal Findings:

The primary outcome, first occurrence of all-cause death or HF readmission by day 180, for the high-intensity care group vs. usual care group, was: 15.2% vs. 23.3% (p = 0.0021).

The secondary outcome for high-intensity care group vs. usual care group:

  • All-cause death or HF readmission by day 90: 10.4% vs. 13.8% (p = 0.08)
  • All-cause death by day 180: 8.5% vs. 10.0% (p = 0.42)
  • Change in baseline to day 90 EQ-5D visual analogue scale: 0.88 vs. 0.90 (p < 0.0001)
  • HF readmission by day 180: 9.5% vs. 17.1% (p = 0.0011)
  • Adjusted mean change in systolic blood pressure by day 90: -3.7 vs. 1.6 mm Hg (p < 0.0001)
  • Adjusted mean change in body weight by day 90: -1.78 vs. -0.42 kg (p < 0.0001)
  • Adjusted ratio of geometric mean of NT-proBNP: 0.44 vs. 0.56 (p = 0.0003)


The results of this trial show that, among patients with hospitalization for acute decompensated HF, rapid up-titration of HF treatments in a high-intensity care model was safe and associated with a reduced risk of death or being readmitted for HF at 180 days. The trial did not show reductions in all-cause death at 180 days, but this study was likely underpowered to detect such a difference. Improvements in quality of life, blood pressure, and body weight were also noted. Serious adverse events were similar. The reductions in readmission and improvements in quality of life are of value in the HF population given the substantial burden of disease and the morbidity associated with hospital stays. With the advent of newer classes of HF GDMT, there is a push to treatment with optimal doses of GDMT. However, this is poorly accomplished in real-life clinical settings, and the evidence supporting rapid initiation of GDMT was mostly observational. STRONG-HF provides important, rigorous trial evidence showing that high-intensity care of participants with HF to rapidly up-titrate and treat HF.

STRONG-HF was initiated prior to approval of SGLT2 inhibitors for treatment of HF, and this medication class was mostly not used in this trial. However, the findings from this trial will likely also be applicable to early initiation of SGLT2 inhibitors, whose use has been associated with further reductions in HF hospitalization. Finally, it is interesting that the trial also included a subset of participants with HF with preserved EF (HFpEF), where the evidence for medical therapy is much less robust than for patients with HF with reduced EF (HFrEF). Additional analysis evaluating outcomes by baseline LVEF will be important to understand the heterogeneity of the treatment effect of the high-intensity care model.


Mebazaa A, Davison B, Chioncel O, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomized, trial. Lancet 2022;400:1938-52.

Editorial Comment: Cox ZL, Lindenfeld J. STRONG start for implementation of guideline-directed medical therapies. Lancet 2022;400:1901-3.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Body Weight, Heart Failure, Length of Stay, Mineralocorticoid Receptor Antagonists, Natriuretic Peptide, Brain, Neprilysin, Outpatients, Patient Discharge, Patient Readmission, Peptidyl-Dipeptidase A, Quality of Life, Receptors, Angiotensin, Stroke Volume, Ventricular Function, Left

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