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Could empagliflozin become a treatment for heart failure?


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Topline results from the EMPEROR-Preserved Phase 3 trial suggest potential for empagliflozin as a treatment for heart failure with preserved ejection fraction. The as-yet-unpublished findings are due to be presented at the European Society of Cardiology (ESC) Congress 2021 in August.

 
 
 
 

The EMPEROR-Preserved trial investigated the safety and efficacy of the SGLT-2 inhibitor Jardiance® (empagliflozin)in patients with chronic heart failure with preserved ejection fraction (HFpEF) and met its primary endpoint, establishing empagliflozin as ‘the first and only therapy to significantly reduce the risk of the composite of cardiovascular death or hospitalisation for heart failure in adults, with or without diabetes, who live with HFpEF’, according to the announcement from Boehringer Ingelheim and Eli Lilly and Company.

 
 
 
 

It follows the positive results from the EMPEROR-Reduced trial, which investigated the safety and efficacy of Jardiance in patients with chronic heart failure with reduced ejection fraction (HFrEF). It found that Jardiance significantly lowered the combined relative risk of cardiovascular death or hospitalisation for heart failure by 25% compared to placebo.

 
 
 
 

This Phase 3, randomised, parallel-group, double-blind, placebo-controlled trial involved 5988 symptomatic HFpEF patients left ventricular ejection fraction of >40%, who were given 10 mg Jardiance or placebo. The primary endpoint was time to first event of adjudicated cardiovascular death or adjudicated hospitalisation for heart failure. The safety profile was generally consistent with the known safety profile of Jardiance.

 
 
 
 

Jardiance is currently used alongside lifestyle changes to lower blood glucose in adults with type 2 diabetes and also to reduce the risk of cardiovascular death in adults with type 2 diabetes who have cardiovascular disease.

 
 
 
 

Diabetes and heart failure

 
 
 
 

Diabetes and heart failure are risk factors for one another and are often seen together. According to a 2020 paper in Diabetes Therapy (Williams DM, Evans M. Are SGLT-2 inhibitors the future of heart failure treatment? The EMPEROR-Preserved and EMPEROR-Reduced Trials. Diabetes Therapy. 2020. 11:1925-1034. https://doi.org/10/1007/s13300-020-00889-9), the worldwide prevalence of heart failure is substantial and increasing. Diabetes increases the risk of developing it by more than twofold in men and fivefold in women, with an estimated 25% of people with diabetes suffering chronic heart failure.

 
 
 
 

It also highlighted a study in which 45.5% of people with HFpEF and 41.8% with HFrEF were diagnosed with diabetes, respectively.

 
 
 
 

In people with diabetes, it stated that several mechanisms may explain the relatively high risk of HFpEF, including impaired cardiac metabolism and substrate utilisation, altered insulin signalling and cardiac deposition of advanced glycated end products.

 
 
 
 

There is currently no approved therapy that demonstrates an improvement in mortality for people with HFpEF.

 
 
 
 

For more on EMPEROR study results, enroll on our SGLT-2 inhibitors course.

 
 
 
 

The opinions expressed in this article are those of the author, Dr Eleanor D Kennedy.

 
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