Dapagliflozin reduces mortality and hospitalization rates for patients with mild heart failure and reduced ejection fraction

Référence

McMurray JJV, Solomon SD, Inzucchi SE, et al, for the DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019;381(21):1995-2008.

Sommaire

Dapagliflozin is an SGLT2-inhibitor indicated for the treatment of T2DM. These researchers identified 4744 patients with heart failure with a reduced ejection fraction (< 40%); all patients were receiving standard therapy for heart failure. Persons with significant chronic kidney disease or type 1 diabetes were excluded. The study participants were then randomized to receive dapagliflozin 10 mg once daily or placebo. Groups were balanced at baseline, and analysis was by intention to treat. The mean age of participants was 66 years, 23% were women, 30% were of a nonwhite race, and 38% had atrial fibrillation. Interestingly, only 42% had T2DM at baseline. After a median follow-up of 18 months, there were significantly fewer hospitalizations or urgent visits due to heart failure in the treatment group (10.0% vs 13.7%; NNT = 27 over 18 months). All-cause mortality was also significantly lower in the treatment group (11.6% vs 13.9%; NNT = 44 over 18 months). Overall, safety was good, with no clinically important differences between groups. The authors report a subgroup analysis for a composite outcome that inappropriately mixes the minor (an urgent visit for heart failure) with the moderately serious (hospitalization for heart failure) and the most serious (death). Interestingly, there was no difference in the likelihood of this composite outcome between patients with and without T2DM, The benefit was much greater for patients with NYHA class II heart failure (hazard ratio [HR] 0.63; 95% CI 0.52 - 0.75) and was not significant for patients with NYHA class III or IV heart failure (HR 0.90; 0.74 - 1.09). There was a slightly greater improvement on a 100-point heart failure–specific symptom score with active therapy (3 points), but although this is statistically significant it is not clinically significant.