Dr. John McMurray presented the results of the DAPA-HF trial at the American Heart Association 2019 Meeting. The study, which was published in the New England Journal of Medicine, showed that dapagliflozin, an SGLT-2 inhibitor, can potentially be used to treat heart failure with reduced ejection fraction (HFrEF) in patients with and without type 2 diabetes.
Dapagliflozin, a sodium-glucose co-transporter 2, is typically used for the treatment of type 2 diabetes. Previous studies have demonstrated that dapagliflozin can prevent the occurrence of heart failure in patients with type 2 diabetes. However, whether dapagliflozin is efficacious in the treatment of heart failure is not known. In this trial, the investigators aimed to determine whether dapagliflozin can be used to treat heart failure in patients with and without type 2 diabetes mellitus.
DAPA-HF was a randomized trial that randomized patients with heart failure and a reduced ejection fracture in a 1:1 ratio to either dapagliflozin 10mg once daily or placebo. Inclusion criteria included a New York Heart Association heart failure class of II, III and IV; a left ventricular ejection fraction of 40% or less; and an NT-ProBNP level of 600pg/ml or greater. The NT-proBNP cut off was lowered to 400pg/ml if patients were hospitalized for heart failure within the last year. Patients with an estimated glomerular filtration rate of 30ml/min/1.73m2, a systolic blood pressure of less than 95 mmHg or patients with type 1 diabetes were excluded. The primary outcome of the study was cardiovascular death, hospitalization for heart failure, or urgent heart failure visit. Additionally, the investigators wanted to assess whether this effect differed depending on the patient’s diabetic status.
A total of 4,744 patients were enrolled in the study (2,373 in the dapagliflozin group and 2,371 in the placebo group and followed up for a median of 18.2 months. The mean age was 66, 24% had diabetes and 42% had diabetes. The primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (HR 0.74, 95% CI 0.65 to 0.85, P<0.001). When patients were stratified according to their diabetic status, there was no evidence of effect modification (Diabetes: HR 0.75 95% CI 0.63-0.90; No diabetes: HR 0.73, 95% CI 0.60 – 0.88; p-value for interaction = 0.80). There was no evidence of effect modification for all components of the primary outcome. Additionally, more patients in the dapagliflozin group experienced an improvement in symptoms and fewer patients experience a deterioration. This did not differ between the patients with and without diabetes. As for dapagliflozin’s safety profile, dapagliflozin was found to be well tolerated in patients with and without diabetes.
The investigators found that among patients with heart failure, dapagliflozin given at a dose of 10mg daily was effective at reducing the risk of worsening heart failure events and cardiovascular death and improved symptoms in patients with and without diabetes. The study highlights a potentially new treatment approach for the management HFrEF in patients with and without diabetes.