Early effects of SGLT2 inhibitors in acute heart failure: an individual patient-level meta-analysis

BACKGROUND AND AIMS: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective in the treatment of chronic heart failure (HF) and stabilized acute HF. Early clinical effects on decongestion in patients with acute HF remain uncertain. We aimed to evaluate the effect of early SGLT2i treatment on diuresis, in-hospital and post-discharge outcomes in patients with acute HF. METHODS: Individual patient-level data were pooled from randomized controlled trials comparing SGLT2i with placebo/control in patients with acute HF, in which information on diuretic response as a measure of decongestive response was available. The main outcome was 24-h diuresis. Secondary outcomes included diuresis up to Day 5, natriuresis, all-cause mortality, and HF rehospitalization at 30 and 60 days, and a win ratio analysis combining death, HF rehospitalization, and 24-h diuresis. RESULTS: Overall, 623 patients from 6 trials were included. Median age was 67 years, and 38% were female. Compared with placebo/control, patients randomized to SGLT2i showed higher 24-h diuresis 3500 (2038-4650) vs 2700 (1950-3625) ml (P < .001). This effect of SGLT2i on diuresis persisted through Day 5. SGLT2i therapy did not increase natriuresis at any timepoint. The 60-day risk of the composite outcome of all-cause mortality and HF rehospitalization was lower with SGLT2i (adjusted hazard ratio 0.62 (95% CI 0.41-0.95), P-value = .028). The win ratio of the hierarchical endpoint favoured SGLT2i (win ratio: 1.45 (95% CI: 1.16-1.82), P-value = .001). Safety outcomes and subgroup analyses did not differ between groups. CONCLUSION: SGLT2i therapy, initiated early in admission for acute HF, increased diuresis and reduced the risk of post-discharge mortality and HF readmission.