More than 60 million people worldwide have heart failure, with approximately half of them having heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure.
HFpEF has been described as the single largest unmet need in cardiovascular medicine based on prevalence, poor outcomes and the absence of clinically proven therapies to date.
In Malaysia, heart failure is a significant public health issue, affecting 6.7% of the population.
It is the leading cause of hospitalisation for patients over 65 years old, with approximately 30% of patients dying within one year of admission.
Malaysians are more likely to develop heart failure due to prevalent risk factors such as insufficient physical activity (over half of the population) and raised blood glucose levels (10%-11%), among others.
With a five-year death rate at 48%, heart failure is deadlier than many cancers, e.g. colorectal cancer (35.5%), non-Hodgkin’s lymphoma (29.6%) and breast cancer (10%).
Additionally, two-thirds of patients suffer from mobility problems, over three-quarters struggle to carry out their usual activities, and half have anxiety or depression.
“For people with HFpEF, the reality is that, so far, there are no clinically proven treatments we can offer that would make a significant impact on their condition,” said Professor Dr Stefan Anker.
Therefore, the recently-published results from the Emperor-Preserved Phase III clinical trials “brings hope for millions of patients” suffering from this condition, said the Charité Berlin cardiologist and principal investigator for the trial.
Presented at the European Society of Cardiology (ESC) Congress 2021 and published in The New England Journal of Medicine, the trial results showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitor under investigation produced a 21% relative risk reduction in death or hospitalisation for heart failure in HFpEF patients, compared with a placebo.
This was independent of either the patient’s ejection fraction or diabetes status, establishing the SGLT2 inhibitor as the first and only treatment to significantly improve outcomes for the full spectrum of heart failure patients.
The drug also reduced the relative risk of first and recurrent hospitalisations for heart failure by 27%, and significantly slowed kidney function decline.
Said Prof Anker: “The primary endpoint was similarly improved in all subgroups of patients, in men and women, with and without diabetes, and regardless of their ejection fraction and kidney function level.
“This underlines the breadth of the SGLT2 inhibitor’s efficacy and its potential overall impact.”
The Emperor-Preserved trial involved 5,988 people with heart failure.
Of these, 4,005 had a left ventricular ejection fraction (LVEF) of 50% or above, and 1,983 had a LVEF below 50%.
Trial participants were randomly assigned to 10mg of the SGLT2 inhibitor or a placebo once daily.
The overall safety data was consistent with previous findings.
The benefits demonstrated in the Emperor-Preserved trial are similar to those in the Emperor-Reduced trial published last year (2020).
That trial showed that the SGLT2 inhibitor significantly reduced the relative risk of death or hospitalisation for heart failure by 25% in patients with heart failure with reduced ejection fraction (HFrEF), compared with a placebo.
Together, these studies demonstrate the benefits of the SGLT2 inhibitor for patients across the full heart failure spectrum.
This drug is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes.
It is also approved for the treatment of HFrEF patients in the European Union and the United States.
Boehringer Ingelheim, which produces the drug, plans to apply for global regulatory approval for its use in HFpEF this year (2021).
Research is also ongoing into the effects of this SGLT2 inhibitor on hospitalisation for heart failure and death in post-heart attack patients with high risk of heart failure, as well as on chronic kidney disease.