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.

Commentary

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.