New research explores the potential of empagliflozin and sacubitril/valsartan as early treatment after a myocardial infarction

Researchers from the Germans Trias i Pujol Research Institute (IGTP) have conducted a preclinical study on the effects of the drug empagliflozin, alone or in combination with sacubitril/valsartan, in the early phase following a myocardial infarction. The combination of the two showed promising results.

A myocardial infarction, commonly known as a heart attack, remains one of the leading causes of illness and death worldwide. When one occurs, part of the heart muscle is deprived of oxygen due to a blocked artery. This lack of oxygen causes damage to the heart tissue, triggering an inflammatory response to clear away the dead cells and start the healing process.

As part of this response, a collagen-rich scar forms. While this scar is essential for holding the heart together, it cannot contract like healthy heart muscle. Over time, this non-contractile scar tissue can reduce how well the heart pumps blood. It may cause the shape and size of the heart's left ventricle to change in a harmful way and increase the risk of malignant ventricular arrhythmias (dangerous heart rhythm problems). Altogether, these effects can lead to the development of heart failure.

New treatments offering hope for heart recovery

In recent years, new medications such as sacubitril/valsartan and empagliflozin have greatly improved outcomes in patients with established heart failure. Sacubitril/valsartan combines two types of drugs that work together to support the heart by regulating hormones involved in blood pressure and fluid balance, while also helping the body keep natural substances that relax blood vessels and reduce strain on the heart. This helps reduce inflammation, improve the shape and function of the left ventricle and decrease scarring in the heart (myocardial fibrosis). Meanwhile, empagliflozin, originally developed to treat type 2 diabetes, has also been found to protect the heart in several ways. It helps reduce inflammation and oxidative stress, increases the availability of helpful molecules like nitric oxide, optimises how the heart uses energy, and promotes favourable changes in the left ventricle.

Although these treatments have well-established benefits in chronic heart failure, their potential in the acute phase just after a heart attack is still not well understood. To address this gap, researchers from the Heart Failure and Cardiac Regeneration (ICREC) research group at IGTP, together with the Germans Trias Heart Institute (iCor) from Germans Trias i Pujol University Hospital (HUGTiP) conducted a preclinical study using a porcine model of myocardial infarction. They tested how empagliflozin, used on its own or combined with sacubitril/valsartan, might help the heart in the early stages after a heart attack.

Exploring early treatment after a heart attack

The study, recently published in the Journal of the American Heart Association (JAHA), looked at the effects of these interventions after a heart attack, examining inflammation, oxidative stress, metabolism, scar composition, cardiac function and arrhythmogenic risk.

When empagliflozin was used on its own, it showed strong anti-inflammatory effects, such as lowering the number of inflammatory cells in the blood shortly after the heart attack. It also helped increase the availability of nitric oxide and favourably altered the composition of the myocardial scar. However, the treatment with empagliflozin alone did not lead to clear improvements in overall cardiac function or in reducing the risk of ventricular arrhythmias.

In contrast, the combination of empagliflozin with sacubitril/valsartan produced more promising results. It led to less collagen build-up in the scar tissue, reduced remodelling of the left ventricle and a decreased arrhythmogenic substrate, as evidenced by a reduced likelihood of triggering ventricular tachycardia during testing.

Next steps towards clinical application

"These findings validate the anti-inflammatory properties and nitric oxide-enhancing effects of empagliflozin in the context of myocardial infarction, and underscore the potential additive benefits of combining it with sacubitril/valsartan to mitigate adverse structural and electrophysiological remodelling", state Dr Felipe Bisbal and Dr Carolina Gálvez-Montón, principal investigators of the study.

The study forms part of the PhD thesis of Daina Martínez, who recently defended her doctoral research at IGTP. "This project has allowed us to better understand the early mechanisms of cardiac repair and how combining treatments might enhance recovery after a heart attack", she explains.

The authors highlight the need for future clinical trials to confirm these preclinical findings in human subjects and to establish the optimal timing, dosing, and combination strategies for pharmacological intervention following myocardial infarction.