DAPA-HF: The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial

The findings of the Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure Trial (DAPA-HF) suggest that dapagliflozin is effective in the treatment of reduced ejection fraction (HFrEF) in patients with and without type 2 diabetes (T2D).

In this study, researchers randomized 4,744 patients (mean age, 66, 23% female) from 410 centers across 20 countries from February 15, 2017, through August 17, 2018. The population of interest were required to be New York Heart Association (NYHA) functional class II-IV, with a left ventricular ejection fraction (LVEF) of 40% or lower, having a plasma NT-proBNP of at least 600 mg/mL, and undergoing standard drug and device therapy for HF. Overall, 68% of patients were in NYHA class II, mean LVEF was 31% and the median NT-proBNP 1437pg/mL. Also, 56% of patients had an ischemic etiology and 42% had a history of type 2 diabetes (T2D). For the study’s key endpoint, the researchers said that dapagliflozin would need show superiority for the primary composite outcome of a first episode of worsening heart failure (HF) or death from cardiovascular (CV) causes.

The secondary outcomes of this study were defined as: the composite of HF hospitalization or CV death; the total number of recurrent HF hospitalizations (including repeat admissions) and CV deaths; change from baseline to 8-months in the total symptom score of the Kansas City Cardiomyopathy Questionnaire (KCCQ); the incidence of a composite worsening renal function outcome and; and all-cause mortality.

According to the results, dapagliflozin reduced the risk of worsening heart failure events as well as CV mortality while improving symptoms in patients with HFrEF. The researchers reported a reduction in the primary composite outcome in patients with diabetes (HR=0.75; 95% CI, 0.63 to 0.90) and also in patients with no diabetes (HR=0.73; 95% CI, 0.60 to 0.88). Reductions were also observed in the individual components of the primary outcome such as CV death (dapagliflozin lowered risk in both diabetic and non-diabetic cohorts) and worsening HF events (again in both cohorts).

“When added to standard therapy, dapagliflozin reduced the risk of worsening HF events and CV death, and improved symptoms, in patients with HFrEF, both with and without T2D,” John J.V. McMurray, BHF, of the Cardiovascular Research Centre in Glasgow, U.K., concluded in the presentation. “The relative and absolute risk reductions in death and hospitalization were substantial, clinically important, and consistent in patients with and without T2D. Dapagliflozin was well tolerated and the rate of treatment discontinuation was low in patients with and without T2D.”

Dapagliflozin was recently granted a Fast Track designation by the FDA. The designation, according to the manufacturer, allows for the accelerated development and research of dapagliflozin to reduce the risk of CV death or worsening heart failure in adults with heart failure with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF).