Intensive neurohormonal blockade enhances decongestion, reduces mortality in acute heart failure: STRONG-HF analysis

"Intensive uptitration of the neurohormonal blockade resulted in more effective and sustained decongestion by day 90, along with a reduced risk of the primary endpoint, which includes all-cause mortality or heart failure (HF) readmission by day 180," the researchers reported in the Journal of the American College of Cardiology.

Heart failure is a leading cause of morbidity and mortality globally, characterized by fluid overload and a complex interplay of neurohormonal activation. Traditionally, treatment strategies have focused on the medications' gradual titration, including angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, and mineralocorticoid receptor antagonists (MRAs).

Comprehensive uptitration of neurohormonal blockade addresses the underlying mechanisms of congestion and could provide an effective strategy for decongesting patients following acute heart failure. Jan Biegus, Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland, and colleagues tested this hypothesis in the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro–Brain Natriuretic Peptide Testing of Heart Failure Therapies) trial.

In the STRONG-HF trial, AHF patients were randomized to either the high-intensity care (HIC) group, which involved rapid uptitration of the neurohormonal blockade, or the usual care (UC) group. Successful decongestion was defined as an absence of pulmonary rales, peripheral edema, and jugular venous pressure <6 cm.

The analysis led to the following findings:

• At baseline, the same proportion of patients in both arms had successful decongestion (HIC 48% vs UC 46%).
• At day 90, a higher proportion of patients in the HIC arm (75%) experienced successful decongestion versus the UC arm (68%).
• Each separate component of the congestion score was significantly better in the HIC arm.
• Additional markers of decongestion also favored the HIC: weight reduction (adjusted mean difference: −1.36 kg), N-terminal pro–B-type natriuretic peptide level, and lower orthopnea severity.
• More effective decongestion was achieved despite a lower mean daily dose of loop diuretics at day 90 in the HIC arm.
• Among patients with successful decongestion at baseline, those in the HIC arm had a significantly better chance of sustaining decongestion at day 90.
• Successful decongestion in all subjects was associated with a lower risk of 180-day HF readmission or all-cause death (HR: 0.40).

The findings showed a significantly greater decongestion at day 90 despite a significantly lower mean dose of loop diuretics at this time point in patients in the HIC arm. Successful decongestion was linked with a lower risk of heart failure hospitalization and all-cause mortality.

"This is the first evidence that intensive and comprehensive uptitration of the neurohormonal blockade—using ACE inhibitors, ARBs, ARNI, beta-blockers, and MRAs—during the early post-discharge phase in patients with acute heart failure promotes effective decongestion, potentially leading to improved outcomes," the researchers concluded.

Reference:

Biegus, J., Mebazaa, A., Davison, B., Cotter, G., Edwards, C., Čelutkienė, J., Chioncel, O., Cohen-Solal, A., Filippatos, G., Novosadova, M., Sliwa, K., Adamo, M., Arrigo, M., Lam, C. S., Ter Maaten, J. M., Deniau, B., Barros, M., Čerlinskaitė-Bajorė, K., Damasceno, A., . . . Ponikowski, P. (2024). Effects of Rapid Uptitration of Neurohormonal Blockade on Effective, Sustainable Decongestion and Outcomes in STRONG-HF. Journal of the American College of Cardiology, 84(4), 323-336. https://doi.org/10.1016/j.jacc.2024.04.055