Paris, France – 1 Sept 2019: Dapagliflozin reduces death and hospitalisation in patients with heart failure and reduced ejection fraction with and without diabetes. The late breaking results of the DAPA-HF trial are presented in a Hot Line Session today at ESC Congress 2019 together with the World Congress of Cardiology(1).
Principal investigator Professor John McMurray of the University of Glasgow, UK said: “The most important finding of all is the benefit in patients without diabetes. This is truly a treatment for heart failure and not just a drug for diabetes.”
Sodium-glucose cotransporter 2 (SGLT2) inhibitors including dapagliflozin reduce the risk of developing heart failure in patients with type 2 diabetes. The DAPA-HF trial(2,3) investigated whether dapagliflozin was also useful in treating established heart failure, even in patients without diabetes.
The trial enrolled 4,744 patients with heart failure and reduced ejection fraction in 20 countries and randomly allocated them to either dapagliflozin 10 mg once daily or matching placebo. The primary endpoint was the composite of a first episode of worsening heart failure (hospitalisation for heart failure or an urgent heart failure visit requiring intravenous therapy) or death from cardiovascular causes.
The allocated treatments were given on top of standard care: 94% received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker or angiotensin receptor–neprilysin inhibitor; 96% took a beta-blocker; and 71% took a mineralocorticoid receptor antagonist(4).
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 (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.65–0.85; p<0.00001).
The components of the primary outcome were also analysed separately. A total of 237 patients (10.0%) receiving dapagliflozin and 326 patients (13.7%) receiving placebo experienced a first episode of worsening heart failure (HR 0.70; 95% CI 0.59–0.83; p<0.00004) and 227 (9.6%) and 273 (11.5%), respectively, died from cardiovascular causes (HR 0.82; 95% CI 0.69–0.98; p=0.029).
Regarding side effects, 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 renal 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 hypoglycaemia and lower limb amputation and fracture were infrequent and occurred at similar rates in the two treatment groups.
Prof McMurray said: “Adverse events rarely required the discontinuation of treatment. There was no notable excess of any serious adverse event in the dapagliflozin group.”
He concluded: “The trial shows that dapagliflozin reduces death and hospitalisation, and improves health-related quality of life, in patients with heart failure and reduced ejection fraction, with and without diabetes. The clinical implications are potentially huge – few drugs achieve these results in heart failure and dapagliflozin does even when added to excellent standard therapy.”