After hospital admission for acute heart failure (HF), a rapid up-titration of guideline-directed medication is associated with improved symptomology and a reduced risk for all-cause mortality or HF readmission. These findings were published in The Lancet.
The multinational, open-label, randomized, prospective clinical trial STRONG-HF (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies; ClinicalTrials.gov Identifier: NCT03412201) recruited patients (N=1078) hospitalized for acute HF at 87 hospitals in 14 countries. Patients were randomly assigned to receive rapid up-titration (n=542) or standard care (n=536) of guideline-directed β-blockers (BBs) or angiotensin converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), or angiotensin receptor-neprilysin inhibitors (ARNis) plus mineralocorticoid receptor antagonists (MRAs).
For the rapid up-titration group, patients were monitored closely for dose optimization which first occurred within 2 days of anticipated discharge on the basis of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and were reassessed at weeks 1, 2, 3, and 6 after randomization. Safety follow-ups occurred at 1 week following any up titration. All patients were evaluated at 180 days for mortality and HF readmission.
The intervention and control cohorts included patients with a mean age of 62.9 (SD, 13.5) and 63.0 (SD, 13.7) years, 60% and 63% were men, 77% and 77% were White, 67% and 68% had a left ventricular ejection fraction (LVEF) of 40% or less, 26% and 25% had been hospitalized for HF in the previous year, respectively. Prior to randomization, 94% and 96% took MRAs, 38% and 39% took ACEis, 34% and 37% took BBs, 19% and 14% took ARBs, and 8% and 9% took ARNIs, respectively.
Compared with baseline and between groups, the rapid up-titration treatment had a significantly greater effect at 90 days on the following compared with usual care:
- Systolic blood pressure (adjusted mean difference [aMD], -5.4 mm Hg; P <.0001)
- Diastolic blood pressure (aMD, -2.3 mm Hg; P =.0001)
- Heart rate (aMD, -5.8 bpm; P <.0001)
- Bodyweight (aMD, -1.36 kg; P <.0001)
- Respiratory rate (aMD, -0.4 breaths per min; P =.0028)
- Potassium concentration (aMD, 0.15 mmol/L; P <.0001)
- Total bilirubin concentration (aMD, -1.69 mmol/L; P =.011)
- NT-proBNP concentration (adjusted ratio of geometric means, 0.77; P =.0003)
- New York Heart Association class (adjusted odds ratio [aOR], 1.36; P <.0001)
- Peripheral edema (aOR, 1.30; P =.0002)
- Jugular venous pressure (aOR, 1.13; P =.015)
The primary endpoint of all-cause mortality or HF readmission at 180 days occurred among 15.2% of the intervention group compared with 23.3% of the controls (adjusted risk ratio [aRR], 0.66; P =.0021).
In a subgroup analysis, rapid up-titration was generally favored among all patient groups over usual care, especially among the following groups:
- Patients aged 75 years or younger
- Patients with an LVEF of greater than 40% or less than 50%
- Patients with greater than median systolic blood pressure at baseline
- Patients with greater than median NT-proBNP levels at baseline
- Patients with median or below estimated glomerular filtration rate at baseline
- Patients without atrial fibrillation
- Patients living in Europe
- White patients
This study may be limited, as the primary endpoint was amended and enrollment expanded due to low event rates.
“Rapid up-titration of guideline-recommended therapies under close follow-up and monitoring, during and early after discharge from a heart failure hospital admission is safe and results in a reduction of heart failure readmissions or all-cause deaths and improves patients’ quality of life within 180 days,” the study authors wrote.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
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, randomised, trial. Lancet. Published online November 7, 2022. doi:10.1016/S0140-6736(22)02076-1