Contemporary decongestion strategies in acute heart failure: an individual patient data analysis of three randomized controlled trials

AIMS: Recent randomized controlled trials (RCTs) showed improved decongestive response with intensified treatment during hospitalization for acute decompensated heart failure (ADHF). Nevertheless, none demonstrated long-term benefit, possibly due to lack of statistical power. We therefore pooled individual data from three recent RCTs to assess the clinical impact of intensified decongestive therapy. METHODS: Individual patient data from three RCTs evaluating decongestive strategies in ADHF-acetazolamide (ADVOR), hydrochlorothiazide (CLOROTIC), and natriuresis-guided therapy (PUSH-AHF)-were pooled. The primary endpoint was 90-day heart failure (HF) re-hospitalization and/or all-cause mortality (adjusted for sex and trial). Secondary endpoints included 24- and 48-h diuresis, natriuresis, in-hospital mortality, and length of stay (LOS). RESULTS: A total of 1059 patients (mean age 79, 42% female) hospitalized for ADHF were included. Baseline characteristics were similar, except for a higher proportion of men in the intensified treatment arm (63% vs 54%, P = .004). Intensified treatment did not reduce 90-day all-cause mortality and/or HF readmissions (adjusted hazard ratio [HR] 1.03; 95% confidence interval [CI] 0.81-1.30); however, it was associated with lower in-hospital mortality (adjusted odds ratio [OR] 0.55; 95% CI 0.31-0.96; P = .038). Cumulative diuresis and natriuresis was significantly higher in patients with intensified treatment at 24 and 48 h (adjusted P < .001). There was no difference in doubling of serum creatinine at 3 days between the groups (adjusted P = .123). LOS was significantly shorter in patients in the intensified treatment arm (geometric mean of 9 [95% CI 8-9] days vs 10 [95% CI 9-10] days in the placebo group, adjusted P = .002). CONCLUSION: While intensified decongestive strategies in patients hospitalized for ADHF improve diuresis, natriuresis, and reduce LOS, no benefit was observed for post-discharge clinical outcomes. Although a potential reduction in in-hospital mortality was observed, this finding should be considered exploratory and hypothesis-generating.