Breakthrough results for empagliflozin confirm EMPEROR-Preserved as the first successful trial for heart failure with preserved ejection fraction, Boehringer Ingelheim and Eli Lilly and Company have announced.
Full results from the EMPEROR-Preserved trial will be presented at the European Society of Cardiology (ESC) Congress 2021 on 27 August.
“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades," Dr Mikhail Kosiborod, director of cardiometabolic research at Saint Luke's Mid-America Heart Institute, Kansas City, told Medscape Cardiology.
“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don't know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalisations and cardiovascular death, or only one of the two.
“If we see an impressive benefit for reduction of hospitalisations, but not a significant reduction in death, that would still be a huge advance. That's because, to date, we don't have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalisation or improvement in symptoms, function, or quality of life,” said Kosiborod, who wasn't part of EMPEROR-Preserved.
The companies said in a joint statement that the EMPEROR-Preserved Phase III trial met its primary endpoint, establishing empagliflozin as the first 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 heart failure with preserved ejection fraction (HFpEF).
Empagliflozin is an oral, once-daily, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor and the first type 2 diabetes medicine to include cardiovascular death risk reduction data in its label in several countries
When added to the EMPEROR-Reduced trial results, these findings demonstrate empagliflozin’s efficacy in all forms of heart failure, regardless of ejection fraction. The safety profile was generally consistent with the known safety profile of empagliflozin.
“The EMPEROR-Preserved results represent a significant breakthrough in cardiovascular medicine and a new hope for people with HFpEF, which is an increasingly prevalent public health issue. HFpEF has long been the most challenging form of heart failure to treat,” said Professor Stefan Anker, Charité Campus Virchow-Klinikum, Germany, and EMPEROR-Preserved principal investigator. “Building on previous results from the EMPA-REG-OUTCOME trial, and the EMPEROR-Reduced trial in heart failure with reduced ejection fraction, the EMPEROR-Preserved findings demonstrate that empagliflozin reduces cardiovascular death or hospitalisation for heart failure and has the potential to transform the care of people living with heart failure.”
Heart failure poses a significant global disease burden: more than 60 million patients worldwide have heart failure and half of them have HFpEF. HFpEF has been classified as “the single largest unmet need in cardiovascular medicine” based on prevalence, poor outcomes and the absence of clinically proven therapies to date. It is a leading cause of hospitalisation and is becoming increasingly prevalent in Western countries due to ageing populations, the risk of death rising with each hospital admission. Heart failure with left ventricular preserved ejection fraction occurs when the left ventricle of the heart is unable to fill properly, resulting in less blood being pumped to the body.
“Heart failure is a prevalent and life-limiting condition and some 30 million people worldwide have heart failure with preserved ejection fraction,” said Mohammed Al-Tawil, regional managing director and head of Human Pharma, Boehringer Ingelheim Middle East, Turkey and Africa. “There are limited treatment options for patients who have heart failure, especially with preserved ejection fraction, and these results present opportunities to better serve the needs of patients. With the earlier EMPEROR-Reduced trial results, we now have a potential solution that treats the full spectrum on heart failure.”
“Prior to the EMPEROR-Preserved topline results, there were no clinical studies demonstrating reduced risk of heart failure hospitalisations or cardiovascular mortality for all adults for this particular condition. This is a significant milestone with empagliflozin as studies continue to explore its effect across a wider spectrum of cardio-renal-metabolic diseases. With these results, we can look forward to being able to expand the use of empagliflozin in the treatment for heart failure, whether related or unrelated to Type 2 diabetes,” said Dr Mohamed Meshref, medical director for Middle East Turkey and Africa, Boehringer Ingelheim.
These results add to previous findings from the EMPEROR-Reduced Phase III trial, which showed that in patients with heart failure with reduced ejection fraction (HFrEF) with or without Type 2 diabetes, empagliflozin significantly reduced the combined relative risk of cardiovascular death or hospitalisation for heart failure by 25%, compared to placebo. Together, these studies demonstrate the benefits of empagliflozin for patients across the full heart failure spectrum (including HFrEF and HFpEF).
The EMPEROR-Reduced results formed the basis of the recent approval of a new indication for empagliflozin for the treatment of adults with HFrEF by the European Commission. A supplemental New Drug Application (sNDA) for empagliflozin to reduce the risk of cardiovascular death or hospitalisation for heart failure in adults with HFrEF has been submitted to the US Food and Drug Administration (FDA), with a decision expected later this year. Empagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes (additionally in the EU for the treatment of adults with HFrEF).
In South Africa, empagliflozin is currently also indicated in the use of adults with type 2 diabetes who are at an increased cardiovascular risk and to reduce the risk of being admitted to hospital for heart failure.
Empagliflozin is also currently being investigated in chronic kidney disease.
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