ABC Heart Fail Cardiomyop 2022; 2(3): 329-330
Lessons from the EMPEROR Preserved
Ivna Girard Cunha Vieira Lima
, Edimar Alcides Bocchi
In randomized clinical trials, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown effective in reducing the risk of cardiovascular (CV) death and hospitalization for chronic heart failure (CHF), as well as renal outcomes, regardless of the presence of diabetes. Despite these findings in patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), retrospective subanalyses of patients with type 2 diabetes have suggested that many of preventable events have occurred in patients with a left ventricular (LV) EF (LVEF) greater than 40%. In this regard, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) was carried out to evaluate the safety and efficacy of empagliflozin in patients with HFpEF. A total of 5988 patients with LVEF > 40% were randomized (Empagliflozin or placebo) and followed up for a median of 26.2 months; 45% of participants were women, symptomatic, with class II–IV heart failure, one hospitalization in the last year and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels of more than 300 pg/mL if in sinus rhythm or > 900 pg/mL if in atrial fibrillation NT-PRO-BNP. The primary outcome – composite outcome of CV death or hospitalization for heart failure (HF) – occurred in 13.8% in the empagliflozin group and in 17.1% in the placebo group, with a hazard ratio of 0.79; 95% confidence interval (CI) of 0.69 to 0.90; p<0.001. No significant difference was found in CV death (HR 0.91, 95%CI 0.76-1.09), but a significant difference was observed in hospitalization for HF (HR 0.71, 95%CI 0.60-0.83), regardless of the presence of diabetes. However, this beneficial effect of empagliflozin was not detected in patients with EF>60% (HR 0.87, 95%CI 0.69-1.1) in a subgroup analysis and its limitations.
When the outcomes were stratified by EF, 33% of patients had EF between 41 and 49% and the others an EF>50%. No difference in the effect of the medication was seen between patients with EF > 50% and patients with EF<60% or 41-49% (). Empagliflozin was superior to placebo in improving the combined outcome regardless of the presence of diabetes in patients with HFpEF. The effect was strengthened especially by the reduction in hospitalization for CHF rather than in CV mortality, which seems to be independent of baseline EF, even among patients with EF between 50% and 60%. With these results, empagliflozin was approved for the treatment of patients with this profile, and generated enthusiasm in the scientific community. Previous medications such as candesartan, spironolactone and sacubitril-valsartan have shown no or modest beneficial effect, and predominantly in populations with lower EF.
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