On May 5, 2020, the FDA approved the sodium-glucose cotransporter inhibitor, Farxiga (dapagliflozin) oral tablets to diminish the risk of cardiovascular (CV) death and hospitalization in adults with heart failure (HF)  (New York Heart Association class II-IV) with reduced ejection fraction, with and without type 2 diabetes.

Dapagliflozin is already indicated as an adjunct to diet and exercise to enhance glycemic control in adults with type 2 diabetes mellitus and to reduce the risk of hospitalization for HF in adults with type 2 diabetes mellitus and established CV disease or multiple CV risk factors. In a press release, Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research, stated, “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.”

The approval was based on data from the landmark phase III, randomized, double-blind, placebo-controlled DAPA-HF trial, which evaluated the efficacy of dapagliflozin plus standard-of-care therapy for the prevention of CV death or reduction of HF events (N = 4,744). At baseline, 94% of patients were treated with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors (including sacubitril/valsartan 11%); 96% of patients were treated with beta blockers, 71% with mineralocorticoid receptor antagonists, 93% with diuretics, and 26% with an implantable device. In the study, patients were randomized to receive either dapagliflozin 10 mg once daily or placebo. 

The primary composite outcome was the time to first incidence of CV death or worsening HF (hospitalization or an urgent visit resulting in IV therapy for HF). Results demonstrated that dapagliflozin plus standard of care reduced the risk of CV death or deteriorating HF by 26% compared with placebo (primary composite outcome occurred in 386 patients treated with dapagliflozin over a median of 18.2 months vs. 502 patients in the placebo arm [hazard ratio (HR) 0.74; 95% CI, 0.65-0.85; P <.0001]). 

All three components of the primary composite endpoints contributed to the treatment effect. Moreover, dapagliflozin diminished the total number of hospitalizations for HF (first and recurrent) events and CV death, with 567 and 742 total events, respectively, in the dapagliflozin-treated vs. placebo group (rate ratio 0.75; 95% CI, 0.65-0.88; P = .0002). The findings were consistent in patients with or without diabetes. The study also indicated that no new adverse reactions were recognized in the DAPA-HF study. 

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