September 9, 2019 — The drug Dapagliflozin was found to reduce death and hospitalization in patients who have heart failure with reduced ejection fraction (HFrEF)with and without diabetes. The late-breaking results of the DAPA-HF trial were presented in a Hot Line Session at European Society of Cardiology (ESC) 2019 congress together with the World Congress of Cardiology.
“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,” said Principal Investigator Professor John McMurray M.D., MB ChB, FRCP, FESC, FACC, FAHA, FRSE, of the University of Glasgow, U.K.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors including dapagliflozin reduce the risk of developing heart failure in patients with type 2 diabetes. The DAPA-HF trial investigated whether dapagliflozin was also useful in treating established heart failure, even in patients without diabetes.[1]
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 (hospitalization 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.[2]
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 analyzed separately. A total of 237 patients (10%) 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).
“Adverse events rarely required the discontinuation of treatment. There was no notable excess of any serious adverse event in the dapagliflozin group,” McMurray said.
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.
“The trial shows that dapagliflozin reduces death and hospitalization, and improves health-related quality of life, in patients with heart failure and reduced ejection fraction, with and without diabetes," McMurray concluded. "The clinical implications are potentially huge – few drugs achieve these results in heart failure and dapagliflozin does even when added to excellent standard therapy.”
FDA Clears Dapagliflozin to Reduce Heart Failure Hospitalizations — October 2019 update
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