In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2)
reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent
mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients
with established heart failure and a reduced ejection fraction, regardless of the
presence or absence of type 2 diabetes.In this phase 3, placebo-controlled trial,
we 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 dapagliflozin
(at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The
primary outcome was a composite of worsening heart failure (hospitalization or an
urgent visit resulting in intravenous therapy for heart failure) or cardiovascular
death.Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients
(16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo
group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A
first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin
group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI,
0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in
the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio,
0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively,
died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients
with diabetes were similar to those in patients without diabetes. The frequency of
adverse events related to volume depletion, renal dysfunction, and hypoglycemia did
not differ between treatment groups.Among patients with heart failure and a reduced
ejection fraction, the risk of worsening heart failure or death from cardiovascular
causes was lower among those who received dapagliflozin than among those who received
placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca;
DAPA-HF ClinicalTrials.gov number, NCT03036124.).
