The DAPA ACT HF-TIMI 68 trial showed that starting dapagliflozin in hospitalised heart failure (HF) patients did not significantly reduce short-term cardiovascular death or worsening HF compared with placebo. However, when combined with other trial data on SGLT2 inhibitors, the evidence suggests a meaningful benefit.
Background
- HF hospitalisation is the leading cardiovascular cause for admission and is linked to high mortality and complications shortly after discharge.
- Therapy optimisation during hospital stays could improve outcomes, but data on initiating SGLT2 inhibitors in this setting are limited.
- Dapagliflozin (an SGLT2i) was tested for safety and efficacy in reducing early adverse outcomes when started during hospitalisation.
Study Design
- Type: Double-blind, placebo-controlled randomised trial.
- Sites: 210 centres in USA, Canada, Poland, Hungary, Czech Republic.
- Patients: 2,401 adults (median age 69; 33.9% women) hospitalised with HF and fluid overload.
- Intervention: Dapagliflozin 10 mg daily vs. placebo, started 24 hours–14 days post-admission.
- Primary outcome: Composite of cardiovascular death or worsening HF over 2 months.
Results
- Primary outcome:
- Dapagliflozin: 10.9%
- Placebo: 12.7%
- HR 0.86 (95% CI 0.68–1.08; p=0.20) → not statistically significant.
- Components:
- Cardiovascular death: 2.5% vs. 3.1% (HR 0.78)
- Worsening HF: 9.4% vs. 10.3% (HR 0.91)
- All-cause mortality: 3.0% vs. 4.5% (HR 0.66; 95% CI 0.43–1.00)
- Safety: Slightly higher rates of symptomatic hypotension (3.6% vs. 2.2%) and worsening kidney function (5.9% vs. 4.7%) with dapagliflozin.
Meta-Analysis
- Combining DAPA ACT HF-TIMI 68 with two other SGLT2i trials (empagliflozin, sotagliflozin) in 3,527 patients showed:
- Reduced early cardiovascular death or worsening HF (HR 0.71; p=0.012)
- Reduced all-cause mortality (HR 0.57; p=0.001)
Conclusion
- Dapagliflozin alone: Did not significantly improve early outcomes in hospitalised HF patients.
- Across SGLT2i trials: Strong evidence supports early in-hospital initiation to reduce cardiovascular and all-cause mortality.
- Clinical implication: While dapagliflozin’s individual effect was not statistically significant, the collective trial data argue for the broader use of SGLT2 inhibitors during HF hospitalisation.