Effects of Rapid Uptitration of Neurohormonal Blockade on Effective, Sustainable Decongestion and Outcomes in STRONG-HF

Background: Comprehensive uptitration of neurohormonal blockade targets fundamental mechanisms underlying development of congestion and may be an additional approach for decongestion after acute heart failure (AHF). Objectives: This hypothesis was tested 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. Methods: In STRONG-HF, patients with AHF were randomized to the high-intensity care (HIC) arm with fast up-titration of neurohormonal blockade or to usual care (UC). Successful decongestion was defined as an absence of peripheral edema, pulmonary rales, and jugular venous pressure <6 cm. Results: At baseline, the same proportion of patients in both arms had successful decongestion (HIC 48% vs UC 46%; P = 0.52). At day 90, higher proportion of patients in the HIC arm (75%) experienced successful decongestion vs the UC arm (68%) (P = 0.0001). Each separate component of the congestion score was significantly better in the HIC arm (all, P < 0.05). Additional markers of decongestion also favored the HIC: weight reduction (adjusted mean difference: −1.36 kg; 95% CI: −1.92 to −0.79 kg), N-terminal pro–B-type natriuretic peptide level, and lower orthopnea severity (all, P < 0.001). 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; 95% CI: 0.27-0.59; P < 0.0001). Conclusions: In STRONG-HF, intensive uptitration of neurohormonal blockade was associated with more efficient and sustained decongestion at day 90 and a lower risk of the primary endpoint.