Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction

Dapagliflozin [Farxiga(R) (USA); Forxiga(R) (EU)], a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was recently approved in the USA and the EU for the treatment of adults with symptomatic heart failure with reduced ejection fraction (HFrEF). The cardiovascular (CV) benefits of dapagliflozin were first observed in the DECLARE-TIMI 58 trial, in which dapagliflozin 10 mg/day significantly reduced the risk of CV death or hospitalization for HF in patients with type 2 diabetes mellitus (T2DM) who had or were at risk for atherosclerotic CV disease. In the subsequent DAPA-HF trial, dapagliflozin 10 mg/day in addition to standard of care was associated with a significantly lower risk of worsening HF or CV death than placebo in patients with HFrEF, regardless of the presence or absence of T2DM. The benefits of dapagliflozin also remained consistent regardless of background HF therapies. Dapagliflozin was generally well tolerated, with an overall safety profile consistent with its known safety profile in other indications. In conclusion, dapagliflozin is an effective and generally well-tolerated treatment that represents a valuable new addition to the options available for symptomatic HFrEF. Plain Language Summary Heart failure (HF) is a major cause of death and disability. HFrEF occurs when the left ventricular ejection fraction is <= 40%. Conventional treatments for HFrEF include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, hydralazine/isosorbide dinitrate, and ivabradine. Dapagliflozin [Farxiga(R) (USA); Forxiga(R) (EU)] is an SGLT2 inhibitor originally developed for the treatment of T2DM. It was the first SGLT2 inhibitor to be approved for the treatment of adults with symptomatic HFrEF. When added to standard therapy, dapagliflozin significantly reduced the risk of worsening HF or CV death in patients with HFrEF, regardless of whether or not they had T2DM. Moreover, the beneficial effects of dapagliflozin were seen regardless of patients' usual HF medications. Dapagliflozin was generally well tolerated and is a valuable option for the treatment of symptomatic HFrEF.