A practical approach to sequential nephron blockade in acute decompensated heart failure

Change in dyspnea

Diuretic response

Change in NT-proBNP

Length of stay

No difference in any of the primary endpoint events

Lower incidence of a combined endpoint of inhospital worsening of HF, rehospitalization for HF and mortality at 60 days.

Greater urinary output with empagliflozin

Cumulative urinary output over 5 days

25% increase in cumulative urine output over 5 days

Empagliflozin increased diuretic efficiency compared with placebo, with more pronounced decrease in NT-proBNP

Weight loss

Weight loss adjusted per mean daily loop diuretic dose

Change in NT-proBNP

Hemoconcentration

Clinical congestion score

Empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time-points

Greater weight loss at Day 15 was associated with significantly higher probability for clinical benefit at Day 90 (composite endpoint of all-cause death, heart failure events, and a 5- point or greater difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline to 90 days)

Natriuresis after 24 h

Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm

Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide

Successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy

Patients with acetazolamide add-on achieved more frequently successful decongestion both within 3 days after randomization (42.2% vs. 30.5%) and at discharge (78.8% vs. 62.5%).

Acetazolamide led to a greater urinary output and natriuresis

Acetazolamide did not decrease the risk of death or rehospitalization for HF

Change in dyspnea

Change in body weight

Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo, but there were no significant differences in patient-reported dyspnea

Patients allocated to HCTZ showed greater 24-h diuresis and weight loss for each 40 mg of furosemide

There were no differences in mortality or rehospitalizations

Change in NT-proBNP levels from baseline to 96 hours

No significant difference in the log NT-proBNP reduction between the 2 groups

No significant change in clinical congestion score, dyspnea assessment, urinary output, weight change, mortality or rehospitalization for HF.

All-cause mortality

Cardiovascular death or hospitalization for HF

Tolvaptan had no effect on long-term mortality or heart failure–related morbidity

Tolvaptan improved day 1 patient-assessed dyspnea, day 1 body weight, day 7 edema.

Proportion of patients with at least moderate improvement in dyspnea by 7-point Likert scale at both 8 and 24 h, without death or need for rescue therapy within 24 h (defined as responders)

The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32).

Tolvaptan addition resulted in greater weight loss and net fluid loss compared with placebo

7-point change in self-assessed dyspnea at 8 and 16 h

No difference in the primary endpoint of day 1 dyspnea reduction

Tolvaptan led to a significantly greater weight loss and dyspnea reduction at day 3.