SGLT2 inhibitors reduce cardiovascular events in heart failure patients with mildly reduced and preserved ejection fraction

An analysis of over 12,000 patients found that the SGLT2 inhibitors dapagliflozin and empagliflozin reduced cardiovascular death or hospitalization for heart failure by 20% in heart failure patients with mildly reduced ejection fraction and preserved. Late-breaking research is featured in a Hot Line session today at the 2022 ESC Congress.

In two large trials, DELIVER and EMPEROR-Preserved, dapagliflozin and empagliflozin reduced cardiovascular events in patients with heart failure with slightly reduced and preserved ejection fraction compared to placebo. These therapies are recommended for all patients with heart failure with reduced ejection fraction, with lower recommendations for those with mildly reduced or preserved ejection fraction. Uncertainties remain about the effects of these drugs on mortality and in specific heart failure subpopulations with slightly reduced and preserved ejection fraction. However, neither trial was designed or powered to address these issues.

This pre-specified meta-analysis used participant-level data from DELIVER and trial-level data from EMPEROR-Preserved and used harmonized definitions of endpoints and subgroups. The primary endpoint of the meta-analysis was the composite of cardiovascular death or first hospitalization for heart failure. A number of secondary endpoints were assessed, including cardiovascular deaths, all-cause deaths, first and recurrent hospitalizations for heart failure, urgent visits for heart failure (not requiring hospitalization), all-cause hospitalizations and patient-reported outcomes.

Heterogeneity of treatment effects was assessed in 12 subgroups: age, sex, race, body mass index, systolic blood pressure, New York Heart Association class, history of diabetes, history of atrial fibrillation/flutter, hospitalization for heart failure within 12 months, glomerular filtration rate estimates, use of other heart failure medications, and baseline left ventricular ejection fraction.

The analysis included 12,251 heart failure patients with mildly reduced and preserved ejection fraction who were followed for a median of 2.2 to 2.3 years. The average age of the participants was 72 years old and 44% were women. SGLT2 inhibitors reduced the risk of the primary outcome by 20% (relative risk [HR] 0.80; 95% confidence interval [CI] 0.73-0.87; p

For secondary endpoints, SGLT2 inhibitors reduced total heart failure hospitalizations (including first and recurrent) by 27%, heart failure emergency visits by 35%, and heart failure hospitalizations all causes by 7%. The drugs improved several domains of health-related quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire. There was no significant effect on all-cause mortality and no serious adverse safety signals were identified in either trial. Treatment effects were consistent across 12 subgroups, including patients at the higher end of the ejection fraction spectrum and those previously treated with other heart failure medications.

This meta-analysis summarizes the totality of evidence on SGLT2 inhibitors in patients with heart failure with a left ventricular ejection fraction greater than 40% and supports their use as a cornerstone therapy in this population. »

Dr Muthiah Vaduganathan, Study Author, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA


European Society of Cardiology (ESC)