Dapagliflozin, a drug that is already used to successfully treat type 2 diabetes (T2DM) and prevent development of heart failure (HF), can also be used to treat pre-existing HF, even in patients without T2DM. These are the conclusions of research presented at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September), and simultaneously published in the New England Journal of Medicine (NEJM).

Dapagliflozin is one of the relatively new class of diabetes drugs called Sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Previous studies have shown that SGLT-2 inhibitors not only help regulate glucose levels, but can also improve a number of CV outcomes, including promoting weight loss, reducing blood pressure and reducing the risk of CV mortality. Dapagliflozin has already been proven to reduce the risk of developing HF in patients with T2DM. In this new study, the investigators analyzed whether the drug could also be used to treat patients with T2D with established HF, and also in patients without T2DM.

The DAPA-HF study enrolled 4,744 patients with HF and reduced ejection fraction (HFrEF) in 20 countries, of whom 45% had T2D, and 55% did not have T2D. Patients were randomly allocated to either dapagliflozin 10 mg once daily or matching placebo. The primary endpoint was a combination of a first episode of worsening HF (hospitalization for HF or an urgent HF visit requiring intravenous therapy) or death from CV causes. The treatments in the study were given on top of standard care: 94% received an ACE inhibitor or ARNI; 96% took a beta-blocker; and 71% took an MRA.

The researchers found that, over a median follow-up of 18.2 months, the primary outcome occurred in 386 of 2,373 patients (16.3%) in the dapagliflozin group and in 502 of 2,371 patients (21.2%) in the placebo group, translating to a 26% reduced risk with dapagliflozin (HR: 0.74, 95%CI: 0.65–0.85, p<0.00001). The results were similar in the groups with T2D (HR 0.75) and without T2D (HR 0.73).

The components of the primary outcome were also analyzed separately. A total of 237 patients (10.0%) receiving dapagliflozin and 326 patients (13.7%) receiving placebo experienced a first episode of worsening HF, showing a 30% reduced risk in the dapagliflozin group (HR 0.70; 95% CI 0.59–0.83; p<0.00004). And 227 (9.6%) and 273 (11.5%), respectively, died from CV causes, meaning an 18% lower risk in the dapagliflozin group (HR 0.82; 95% CI 0.69–0.98; p=0.03). All-cause mortality was reduced by 17% (HR 0.83, 95%CI 0.71-0.97; p=0.22). Symptoms, as assessed by the Kansas City Cardiomyopathy Questionnaire were also improved (p<0.001).

178 Patients (7.5%) in the dapagliflozin group had an adverse event related to volume depletion, compared to 162 (6.8%) in the placebo group, with no significant difference between groups. Adverse events related to kidney dysfunction occurred in 153 patients (6.5%) in the dapagliflozin group versus 170 patients (7.2%) in the placebo group, with no significant difference between groups. Major hypoglycemia and lower limb amputation and fracture were infrequent and occurred at similar rates in the two treatment groups.

Source: Press release EASD September 18, 2019

The DAPA-HF results were simultaneously published in The Lancet See also our reporting on DAPA-HF presented at ESC 2019