Contemporary decongestion strategies in acute heart failure: an individual patient data analysis of three randomized controlled trials
L E E C Zonneveld, P Martens, J C Trullas, I E Beldhuis, K Damman, W Mullens, J M Ter MaatenAbstract
Background
several randomized controlled trials (RCTs) have recently shown improved decongestion using an intensified approach during hospitalization for decompensated heart failure (DHF). None of these trials however demonstrated improved long-term clinical outcomes, possibly due to lack of power. We therefore studied the clinical impact of intensified decongestive therapies by pooling individual patient-level data from three RCTs.
Methods
Data from three RCTs investigating different decongestive strategies - natriuresis-guided therapy (PUSH-AHF), acetazolamide (ADVOR) and hydrochlorothiazide (CLOROTIC) – in DHF were pooled for analysis. The primary endpoint was a composite of heart failure (HF) rehospitalization and all-cause mortality at 90 days (adjusted for sex and trial). Secondary endpoints include diuresis, natriuresis, in-hospital mortality and length of stay (LOS).
Results
A total of 1059 patients (mean age 79, 42% female) hospitalized for DHF were included. Baseline characteristics were balanced between the groups, with the exception of a higher proportion of male patients in the intervention arm (63% versus 54%, p=0.004). Patients in the intervention arm had a significantly reduced risk of in-hospital mortality (adjusted OR 0.55; 95% CI 0.31-0.96; p=0.038), while post-discharge clinical outcomes did not differ between groups (adjusted HR 1.03: 95% CI 0.81-1.30 for the combined outcome at 90 days). Cumulative diuresis was significantly higher in patients in the intervention arm at 24- and 48-hours (adjusted p<0.001). A similar treatment effect was seen for natriuresis at the same time points (adjusted p<0.001). There was no difference in doubling of serum creatinine between the groups (p=0.116). LOS was significantly shorter in patients in the intervention arm (geometric mean of 8.5 (95% CI 8-9) days versus 9.8 (95% CI 9.2-10.4) days in the placebo group, p<0.001.
Conclusion
While intensified decongestive strategies in patients hospitalized for DHF improve diuresis, natriuresis, in-hospital mortality, and LOS no benefit was observed for post-discharge clinical outcomes.For image description, please refer to the figure legend and surrounding text.