FDA Approves Dapagliflozin to treat HFrEF

May 6, 2020

The SGLT-2 inhibitor is the first in its class to be approved for the treatment of adults with NYHA class II, III, or IV heart failure with reduced (≤40%) ejection fraction.

The US Food and Drug Administration (FDA) on Tuesday approved dapagliflozin (Farxiga, AstraZeneca [AZ]) to reduce risk of cardiovascular (CV) death and hospitalization in adults with heart failure with reduced ejection fraction (HFrEF), with and without type 2 diabetes (T2D), according to an agency press release.

The approval makes the sodium-glucose co-transport-2 (SGLT-2) inhibitor the first in its class to be approved to treat adults with New York Heart Association class II, III, and IV IV HFrEF.

Landmark trial

FDA's decision, after granting the AZ supplemental new drug application Priority Review designation, was based on findings of a subanalysis of the phase III randomized, placebo-controlled DAPA-HF trial.

DAPA-HF researchers randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either 10 mg dapagliflozin/day or placebo, on a background of prescribed therapy. The majority of participants were male and mean age was 66 years.

The primary outcome was a composite of worsening HF or CV death.

Over a median follow-up of 18.2 months, the primary outcome occurred in 16.3% of patients treated with dapagliflozin and 21.2% of patients treated with placebo (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<.001).

The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups, according to the study.2 A full listing of dapagliflozin side effects can be found here.

“Heart failure is a serious health condition that contributes to one in eight deaths in the US and impacts nearly 6.5 million Americans,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research, in the release. “This approval provides patients with heart failure with reduced ejection fraction an additional treatment option that can improve survival and reduce the need for hospitalization.”

Dapagliflozin is also approved as an adjunct to diet and exercise to improve glycemic control in adults with T2D. In October 2019, dapagliflozin was approved to reduce the risk of hospitalization for patients with HF who have T2D and established CV disease or multiple CV risk factors, according to the FDA release.