Immediate and short-term outcomes of in-hospital canagliflozin initiation in acute heart failure: Results from the CANA-AHF randomized clinical trial.

Background: Early initiation of empagliflozin, a sodium-glucose cotransporter 2 inhibitor, in acute heart failure (AHF) patients increases urine output, reduces hospital stays, and enhances quality of life post-hospital discharge.

Objectives: This trial aims to investigate the effectiveness and safety of early canagliflozin initiation compared to empagliflozin in hospitalized AHF patients with volume overload.

Methods: This was a multicenter, prospective, open-labeled, randomized equivalence trial. AHF diabetic and non-diabetic patients were randomized within 24 h from hospital admission to either receive 100 mg canagliflozin or 10 mg empagliflozin in addition to the standardized protocol for an intravenous loop diuretic. The primary outcome was the median of daily diuresis during the hospitalization period.

Results: Hospitalized AHF patients were enrolled (71 patients per group). The median daily diuresis during the hospitalization period was 4200 ml in the canagliflozin group, which was statistically equivalent to empagliflozin (4117 ml) with a difference of 83 ml, which falls within the predefined equivalence margin (±10) % of the median of daily diuresis of empagliflozin; Δ = ±411.7 mL), confirming equivalence via bootstrap TSOT p < 0.001. No difference was observed in diuretic response, dyspnea score, orthodema congestion score or length of hospital stay. The NT-proBNP level at day 30 post-discharge and the change in KCCQ-TSS from baseline to day 90 were statistically comparable between both groups, without differences in safety event incidence.

Conclusion: Canagliflozin could be a part of usual care for hospitalized AHF patients and an alternative to empagliflozin without safety concerns.