Uptitrating Treatment After Heart Failure Hospitalization Across the Spectrum of Left Ventricular Ejection Fraction

Rachel Balk, PharmD ,M Health Fairview

Background: Acute heart failure (AHF) has long been associated with poor outcomes, rehospitalization, and mortality in heart failure (HF) patients. However, a notable advancement emerged with the publication of the STRONG-HF trial in December 2022. The STRONG-HF trial showed that a high-intensity care treatment strategy, consisting of rapid uptitration of oral HF medications and close follow-up with multiple early ambulatory visits, improved patient quality of life and reduced 180-day all-cause death or HF rehospitalization compared to usual care. Because left ventricular ejection fraction (LVEF) is a baseline measure of cardiac function, it may be reasonable to use it as a predictor for response to high-intensity care versus usual care after hospitalization for AHF.

Objective: To assess the impact of baseline LVEF on high-intensity care versus usual care in the STRONG-HF trial.

Study Design: This was an international, multi-center, open-label, randomized trial that examined rapid uptitration of beta blockers, renin-angiotensin receptor modulators (ACE inhibitors, ARBs, ARNIs), and MRAs versus usual care previously reported in the STRONG-HF trial. The study included 1078 patients, ages 18 to 85, who were admitted for AHF with suboptimal doses of oral HF medications. Inclusion criteria were hospitalization within 72 hours of screening for AHF, hemodynamic stability, and high N-terminal pro-B-type natriuretic peptide. Patients were not excluded based on LVEF but were recorded as being above or less than or equal to 40%. Study endpoints included a primary endpoint of the composite of first HF rehospitalization or all-cause death at day 180 and secondary endpoints of change in EQ-5D visual analog scale from baseline to day 90, 180-day all cause death, and the composite of first HF rehospitalization or all-cause death at day 90. A safety endpoint included was the 90-day incidence of treatment-emergent adverse events and was monitored via changes from baseline in vital signs (blood pressure, heart rate, and body weight) at each visit and laboratory results.

Results: Patients enrolled were stratified based on LVEF: 68% (731/1078) in LVEF ≤40% and 32% (347/1078) in LVEF>40%. Clinical outcomes included an absolute risk reduction of the primary composite endpoint at 180 days in the overall study population of 8.1% (95% CI,2.9%-13.2%; P=0.0021) for high-intensity care versus usual care. Treatment benefit of high-intensity care versus usual care was consistent across reported LVEFs. The EQ-5D visual analog scale change from baseline to day 90 was slightly higher for those with higher LVEF values, but no significant difference when considering LVEF as a continuous variable. Adverse event incidence was similar between LVEF groups and incidence of all events was not significant (P=0.547).

Conclusions: The role of rapid uptitration of oral HF medications in addition to close ambulatory follow-up after AHF hospitalizations in reducing rehospitalization and 180-day mortality is independent of LVEF.

Key Points: Authors stressed the importance of rapid up-titration of oral HF medications paired with close follow-up was independent of LVEF when analyzing rate of rehospitalization and 180-day mortality. Some limitations of this study were carried-over from the STRONG-HF trial, which was a precursor for this study, in that sodium-glucose cotransporter inhibitors were not yet indicated during study design and were not included despite the current indication.


Pagnesi M, Metra M, Cohen-Solal A, et al. Uptitrating treatment after heart failure hospitalization across the spectrum of left ventricular ejection fraction. J Am Coll Cardiol. 2023; Jun, 81(22): 2131–2144. https://doi.org/10.1016/j.jacc.2023.03.426

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.