Dapagliflozin associated with improved outcomes for HF with mildly reduced or preserved ejection fraction
An industry-funded study found patients with heart failure (HF) and an ejection fraction above 40% had a lower combined risk for worsening HF or cardiovascular death if they were randomly assigned to receive dapagliflozin versus placebo.
Patients with chronic heart failure and mildly reduced or preserved ejection fraction may benefit from taking dapagliflozin, according to a new study.
In the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) Trial, 6,263 patients with heart failure and a left ventricular ejection fraction of more than 40% were randomly assigned to receive dapagliflozin (10 mg once daily) or matching placebo in addition to usual therapy. The primary outcome was a composite of worsening heart failure (defined as an unplanned hospitalization or urgent visit for heart failure) or cardiovascular death. The results of the trial, which was funded by AstraZeneca, were published Aug. 27 by the New England Journal of Medicine.
Patients were followed for a median of 2.3 years. The primary outcome occurred in 512 of 3,131 patients in the dapagliflozin group and 610 of 3,132 patients in the placebo group (16.4% vs. 19.5%; hazard ratio [HR], 0.82 [95% CI, 0.73 to 0.92]; P<0.001). Heart failure worsened in 11.8% of the dapagliflozin group and 14.5% of the placebo group (HR, 0.79; 95% CI, 0.69 to 0.91), and 7.4% and 8.3% of patients, respectively, experienced cardiovascular death (HR, 0.88; 95% CI, 0.74 to 1.05). Patients in the dapagliflozin group had fewer total events and lower symptom burden than those in the placebo group. Results were similar in subgroup analyses by left ventricular ejection fraction above or below 60%, presence of diabetes, and history of ejection fraction improving from below 40% to above 40%. Serious adverse event rates were 43.5% in the dapagliflozin group and 45.5% in the placebo group; in each group, 5.8% of patients had adverse events that led to discontinuation of dapagliflozin or placebo.
The researchers noted that fewer than 5% of patients enrolled in the trial were Black and that assessment of symptom burden was restricted by the COVID-19 pandemic, among other limitations. They concluded that dapagliflozin was associated with lower risk for worsening heart failure or cardiovascular death and lower symptom burden and did not increase adverse events. “These data provide further evidence to support the use of an SGLT2 [sodium-glucose cotransporter-2] inhibitor as essential therapy in patients with heart failure, regardless of the presence or absence of type 2 diabetes mellitus or left ventricular ejection fraction,” they wrote.
An accompanying editorial called for additional research on the effects of dapagliflozin on heart failure with preserved ejection fraction in Black patients and patients with cardiomyopathies. “Finally, there is a need to better define the mechanisms by which SGLT2 inhibitors provide therapeutic benefit among patients with heart failure and a preserved ejection fraction. Because SGLT2 inhibitors were developed as hypoglycemic agents and were fortuitously found to improve cardiovascular outcomes during postmarketing safety trials, trials that are designed to define the mechanisms that result in cardiovascular benefits have lagged behind those designed to show improved clinical outcomes,” the editorialist wrote. “From this perspective, the impressive and accumulating clinical successes with SGLT2 inhibitors are both inspiring and humbling.”