Empagliflozin reduces hospitalization for heart failure with preserved ejection fraction (NNT = 59 per year), but not mortality outcomes (EMPEROR-Preserved)

Reference

Anker SD, Butler J, Filippatos G, et al, for the EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021;385(16):1451-1461.

Synopsis

This industry-sponsored trial identified patients with New York Heart Association Class II–IV heart failure, an ejection fraction of at least 40%, and an NT-proBNP level greater than 300 pg/mL (> 900 pg/mL if the patient had atrial fibrillation). Of the 11,583 patients at 622 centers in 23 countries who were screened for the trial, 5988 were ultimately randomized to receive empagliflozin 10 mg once daily or placebo. The primary reason for exclusion was failure to meet the NT-proBNP target. Groups were balanced at the beginning of the study: a mean age of 72 years, 82% with Class II heart failure with a preserved ejection fraction, and approximately one third in each group with ejection fractions from 40% up to 50%, from 50% up to 60%, and 60% or higher. Analysis was by intention to treat, with 77% of patients completing the trial with a median follow-up of 26 months. For the remainder of the patients, the trial medication was stopped for a reason other than death — presumably due to adverse events, although this is not specified by the authors. The primary outcome was a composite of cardiovascular death or hospitalization due to heart failure. Hospitalization for heart failure occurred less often in patients randomized to receive empagliflozin (4.3 vs 6.0 per 100 person-years; hazard ratio [HR] 0.71; 95% CI 0.60 - 0.83; number needed to treat [NNT] = 59 per year). In an exploratory subgroup analysis, benefit was greater for those with lower ejection fractions. There was no significant difference in the likelihood of cardiovascular death (3.4 vs 3.8 per 100 person-years) or all-cause mortality (6.6 vs 6.7 per 100 person-years), and no significant differences in renal outcomes or hospitalization for any cause. There were 20 excess non-cardiovascular deaths in the empagliflozin group, most often due to infection or sepsis, compared with 25 fewer cardiovascular deaths in that group. Hypotension and genital infections were more common in the empagliflozin group.