The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was found to lower the risk for worsening heart failure or death in patients with heart failure and reduced ejection fraction, and with or without diabetes compared with placebo, according to a study published in The New England Journal of Medicine.

In this phase 3 trial ( identifier: NCT03036124), 4744 patients from 410 centers in 20 countries with New York Heart Association functional class II, III, or IV symptom, and an ejection fraction ≤40% were randomly assigned to receive dapagliflozin (n=2373; 10 mg daily) or placebo (n=2371). The participants were stratified according to their type 2 diabetes diagnosis (42% in each group). The study’s median follow-up was 18.2 months.

The study’s primary outcome was a composite of worsening heart failure (hospitalization or urgent visit leading to intravenous heart failure therapy) or cardiovascular death.

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A total of 386 patients (16.3%) and 502 participants (21.2%)  receiving dapagliflozin and placebo, respectively experienced a primary outcome (P <.001), with heart failure occurring in 231 patients (9.7%) and 318 patients (13.4%) receiving dapagliflozin and placebo, respectively (hazard ratio [HR], 0.70; 95% CI, 0.59-0.83), and in and cardiovascular death occurring in 227 patients (9.6%) and 273 patients (11.5%) treated with dapagliflozin and placebo, respectively (hazard ratio [HR], 0.82; 95% CI, 0.69-0.98).

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The rates of discontinuation and adverse outcomes (eg, volume depletion, renal adverse event) were comparable in participants treated with dapagliflozin or placebo (discontinuation: 4.7% vs 4.9%, respectively).

A secondary outcome, the total symptom score on the Kansas City Cardiomyopathy Questionnaire (scale, 0-100; with higher scores associated with fewer symptoms), was found to be higher in participants receiving dapagliflozin vs placebo at the 8-month follow-up compared with baseline (clinically meaningful 5-point increase: 58.3% vs 50.9%, respectively; odds ratio, 1.15; 95% CI, 1.08-1.23).

Study limitations include the relative homogeneity of the cohort (<5% blacks; few elderly or with multiple comorbidities), and the exclusion and inclusion criteria for participant selection, which may limit the generalizability of the results.

“Dapagliflozin was as effective in the 55% of patients without type 2 diabetes as in those with diabetes. This demonstration of the cardiovascular benefits of an SGLT2 inhibitor in patients without diabetes provides support for prior suggestions that such treatment has beneficial actions other than glucose lowering,” noted the study authors. “Thus, our findings potentially extend the therapeutic role of dapagliflozin beyond patients with diabetes.”

Conflict of Interest Disclosure

The study was funded by Astra Zeneca, which manufactures dapagliflozin.


Mcmurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019. doi: 10.1056/NEJMoa1911303