Dapagliflozin Benefits Heart Failure Patients, With or Without Diabetes

The type 2 diabetes drug dapagliflozin reduces the risk for worsening heart failure or death from cardiovascular disease among individuals with heart failure and reduced ejection fraction, whether or not they have diabetes, shows a study published in the New England Journal of Medicine.  (©RawPixel,AdobeStock_191953491).

The type 2 diabetes drug dapagliflozin reduces the risk for worsening heart failure or death from cardiovascular disease among individuals with heart failure and reduced ejection fraction, whether or not they have diabetes, shows a study published in the New England Journal of Medicine.

Dapagliflozin (Farxiga, AstraZeneca) is a sodium glucose cotransporter-2 (SGLT-2) inhibitor approved for glucose-lowering along with diet and exercise in adults with type 2 diabetes.

The findings come from the prospective, phase three, placebo-controlled DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) study  published online September 19 and simultaneously presented at annual meeting of the European Association for the Study of Diabetes held in September in Barcelona. The data were also presented at the Heart Failure Society meeting in Philadelphia the week prior to publication.  

Previous clinical trials have shown that SGLT2 inhibitors including dapagliflozin reduce the risk of hospitalization for heart failure in patients with diabetes without heart failure at baseline. Now, DAPA-HF has shown that the drug benefits patients with heart failure, with similar results in the 55 percent of patients with diabetes as in the 45 percent without. 

“This demonstration of the cardiovascular benefits of an SGLT2 inhibitor in patients without diabetes provides support for prior suggestions that such treatment has beneficial actions other than glucose lowering. Thus, our findings potentially extend the therapeutic role of dapagliflozin beyond patients with diabetes,” wrote John J.V. McMurray, M.D., of the BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom, and colleagues.

In an accompanying editorial, James C. Fang, M.D., of the University of Utah Health, Salt Lake City, called the DAPA-HF results “important and impressive, especially since they substantiate observations from previous trials of SGLT2 inhibitors.”

But, Dr. Fang also questioned whether clinicians would incorporate the findings into daily practice, noting “That remains to be seen, since there are barriers to the use of additional drugs in patients with heart failure, despite the evidence of benefit.”

Those barriers, he said, include concerns about potential side effects of complex medical regimens, unanticipated drug interactions, and challenges with adherence, as well as administrative hurdles and drug costs.

THE STUDY

In DAPA-HF, 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40 percent or less at 410 centers in 20 countries were randomly assigned to receive either 10mg/day of dapagliflozin or placebo, along with recommended therapies. At baseline, 42 percent of each group had a history of type 2 diabetes and another 3 percent per group were newly-diagnosed with it.

The primary outcome, a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death, occurred 16.3 percent in the dapagliflozin group and 21.2 percent of the placebo group, a significant difference with hazard ratio 0.74 and P<0.001.

Both components of the composite outcome favored dapagliflozin, with a 30 percent reduction in hospitalizations for heart failure and a 12 percent reduction in death due to cardiovascular causes. The number of patients who would need to have been treated with dapagliflozin to prevent one primary event was 21.

Dapagliflozin’s effect on the primary outcome remained consistent across prespecified subgroups, although the benefit appeared to be less among patients in New York Heart Association functional class three or four compared to class two. 

“The observed benefits, which were substantial and clinically significant, occurred early after randomization and were seen in patients who were receiving other recommended therapies for heart failure,” the authors wrote.
Few patients stopped dapagliflozin or placebo because of adverse effects ( less than 5 percent in both groups). Major hypoglycemia and diabetic ketoacidosis were rare.

DISCLOSURES
This study was funded by AstraZeneca

REFERENCE
McMurray JJV, Solomon SD, Inzucchi SE, et al. “DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.” N Engl J Med. 2019 Sep 19. doi: 10.1056/NEJMoa1911303. [Epub ahead of print]