New research indicates that a combination of two drugs, empagliflozin and sacubitril/valsartan, may offer benefits when administered early after a heart attack. A preclinical study explored the effects of these drugs on heart recovery.

A myocardial infarction, commonly known as a heart attack, occurs when a blocked artery deprives part of the heart muscle of oxygen. This leads to tissue damage and an inflammatory response.

As the heart heals, a scar forms, composed primarily of collagen. While this scar is crucial for structural integrity, it lacks the contractile properties of healthy heart muscle. Over time, this can impair the heart’s pumping efficiency, perhaps leading to adverse changes in the left ventricle and increasing the risk of hazardous heart rhythm problems, ultimately contributing to heart failure.

Novel Approaches to Cardiac Repair

Recent advances in medication, including sacubitril/valsartan and empagliflozin, have significantly improved outcomes for individuals with established heart failure. Sacubitril/valsartan is a combination medication that supports heart function by regulating hormones involved in blood pressure and fluid balance. It also helps the body preserve natural substances that relax blood vessels and ease strain on the heart, reducing inflammation and myocardial fibrosis, and improving the shape and function of the left ventricle.

Empagliflozin, initially developed for type 2 diabetes, has demonstrated cardioprotective effects. It reduces inflammation and oxidative stress, increases nitric oxide availability, optimizes cardiac energy utilization, and promotes beneficial changes in the left ventricle.

While these treatments are known to benefit chronic heart failure, their potential in the acute phase following a heart attack remains under examination. To address this, researchers conducted a preclinical study using a porcine model of myocardial infarction to assess the impact of empagliflozin, alone or combined with sacubitril/valsartan, on early heart recovery after a heart attack.

Investigating Early Intervention After Myocardial Infarction

The study, published in the Journal of the American Heart Association, evaluated the effects of these treatments on inflammation, oxidative stress, metabolism, scar composition, cardiac function, and arrhythmogenic risk following a heart attack.

Empagliflozin, when administered alone, exhibited anti-inflammatory properties, reducing the number of inflammatory cells in the blood soon after the heart attack. It also increased nitric oxide availability and positively influenced myocardial scar composition.However, empagliflozin alone did not significantly improve overall cardiac function or reduce the risk of ventricular arrhythmias.

The combination of empagliflozin with sacubitril/valsartan yielded more encouraging results. It reduced collagen buildup in the scar tissue, lessened remodeling of the left ventricle, and decreased arrhythmogenic substrate, as indicated by a lower likelihood of inducing ventricular tachycardia during testing.

Future Directions and clinical Relevance

According to Dr. Felipe Bisbal and Dr. carolina Gálvez-Montón, principal investigators of the study, “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 remodeling.”

Daina Martínez, who recently defended her doctoral research, stated, “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.”

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