Study Summary

The DAPA-HF trial evaluated the efficacy of the SGLT2 inhibitor dapagliflozin in reducing cardiac outcomes in patients with HFrEF (LVEF £40%) irrespective of diabetes status. Patients were randomly assigned to receive 10 mg of dapagliflozin (n = 2,373) or placebo (n = 2,371) daily. During follow-up (median 18.2 months), the incidence of the primary composite outcome of first episode of worsening HF ( hospitalization or an urgent care HF visit) or cardiovascular death was 26% lower in the dapagliflozin group than in the placebo group (HR 0.74; P <0.00001). The primary outcome results were similar when stratified by diabetes status. There was a 30% reduction in the occurrence of worsening HF (HR 0.70; P <0.00004), and an 18% reduction in cardiovascular death (HR 0.82; P <0.028) with dapagliflozin compared with placebo. Rates of adverse events — including volume depletion, renal dysfunction, major hypoglycemia, and lower limb amputation — were similar between the groups.


Study Strengths: DAPA-HF is the first trial in which the efficacy of an SGLT2 inhibitor in reducing cardiac outcomes has been evaluated in patients with HFrEF regardless of diabetes status. Previous studies demonstrating a reduction in HF-related hospitalizations with SGLT2 inhibitors only included patients with type 2 diabetes and most did not have HF.

Study Limitations: No comments can be made as the manuscript has not yet been published.

Next Steps/Clinical Perspective: The DAPA-HF trial is a landmark study. If the results are corroborated, dapagliflozin may be considered an effective medication for the secondary prevention of HFrEF, rather than solely as a treatment for diabetes. The benefits of dapagliflozin were seen in patients who were already taking guideline-recommended medications for HF. This study identifies a new mechanistic approach in the treatment of HFrEF, and results from studies of HFpEF are awaited. Further research is needed to determine whether the findings represent a class effect for SGLT2 inhibitors and whether they are also effective for the primary prevention of HF.

Trial Reference

Presented by John McMurray at the European Society of Cardiology Congress, Paris, France, September 1 2019.