The EMPEROR-Preserved study revealed- for the first time that the SGLT2 inhibitor empagliflozin improves clinical outcomes in patients with heart failure (HF) with preserved ejection fraction.

The empagliflozin study included individuals with HFpEF who were either diabetic or did not have diabetes. In the EMPEROR-Reduced study, empagliflozin also improved clinical outcomes in individuals with HF and reduced ejection fraction, with or without diabetes.

These findings are the first to demonstrate an unambiguous advantage of any medication on major heart failure outcomes in individuals with heart failure but maintained ejection fraction. The New England Journal of Medicine published the EMPEROR-Preserved study.

Findings from EMPEROR-Preserved

Anker and colleagues allocated a total of 5,988 patients (mean age, 72 years; 45% female; 49% with diabetes) who had New York Heart Association (NYHA) class II to IV congestive heart failure (CHF) with an ejection fraction (EF) over 40% to take empagliflozin 10 mg daily or receive a placebo. The main outcome measure was mortality due to CV disease or hospitalisation for HF.

During a median follow-up of 26.2 months, the primary outcome occurred in 13.8 per cent of the empagliflozin group versus 17.1 per cent of the placebo group (HR = 0.79; 95 per cent confidence interval [CI], 0.69-0.9; P.0003; number needed to treat to prevent one event = 31), driven by HF hospitalisation (HR = 0.71; 95 per cent CI, 0.6-0.83).

The findings were consistent in both diabetic and non-diabetic individuals. He noted that the findings did not vary by EF (41% to 49%, 50% to 59%, or 60% or above), with a P-value for the trend of.21. The primary-secondary endpoint, total hospitalisations for HF (first and subsequent), was lower in the empagliflozin group (HR = 0.73; 95 per cent CI, 0.61-0.88; P.0009), according to Anker.

According to the findings, the second secondary outcome, the slope of the decrease in glomerular filtration rate over time, similarly preferred empagliflozin (difference, 1.36 mL/min/1.73m2 per year; P.0001). CV mortality was decreased by 9% in the empagliflozin group, but the reduction was not statistically significant (HR = 0.91; 95 per cent confidence interval [CI], 0.76-1.09).

There was no difference in all-cause mortality between the groups (HR = 1; 95 per cent CI, 0.87-1.15). Empagliflozin group had a greater incidence of simple vaginal and urinary tract infections as well as hypotension than the placebo group, but there was no difference in amputation, ketoacidosis, or hypoglycaemia.

HFpEF's practical problems

The success of the EMPEROR-Preserved trial follows years of inability to demonstrate statistically significant improvements in clinical outcomes in patients with HFpEF treated with other agents, including the CHARM-Preserved trial of candesartan, the PEP-CHF trial of perindopril, the I-PRESERVE trial of irbesartan, the TOPCAT trial of spironolactone, and the PARAGON-HF trial of sacubitril (Entresto, Novartis).

Numerous medications have been shown to be ineffective in this group, although two of them, spironolactone and sacubitril/valsartan, were borderline and showed some promise. Spironolactone was shown to be ineffective in the TOPCAT study. Sacubitril/valsartan was shown to be neutral in the PARAGON-HF study, with a P-value of.059. However, the FDA recently authorised this medication for certain patients with HFpEF owing to a lack of alternative choices.

This is a significant improvement over five years ago when there were no particular treatments for HFpEF and we concentrated on comorbidities such as hypertension, atrial fibrillation, and ischaemic heart disease. Now, we have two distinct classes of treatments that are directed particularly at individuals with HFpEF and should have a significant effect on the disease's course and burden.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.