Intravenous administration of atorvastatin during acute myocardial infarction could become a new therapeutic strategy capable of limiting infarct size in patients with diabetic cardiomyopathy, a heart condition associated with diabetes.
This is suggested by a recent experimental study published in the journal Diabetes and led by Dr. Gemma Vilahur, head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases group at the Sant Pau Research Institute (IR Sant Pau) and researcher at the Spanish Network for Cardiovascular Research (CIBERCV), Carlos III Health Institute.
Atorvastatin is a widely used oral drug for lowering blood cholesterol levels and preventing the development of cardiovascular diseases. In this study, a new formulation of atorvastatin was used to allow intravenous administration during the acute phase of the infarction.
“The study shows, in an animal model of diabetic cardiomyopathy, that early administration of a single intravenous dose of atorvastatin after infarction reduces lesion size, improves cardiac function, and favorably modulates the processes of inflammation, cell death, and fibrosis that are triggered in the diabetic heart,” explains Dr. Vilahur.
People with diabetes mellitus have a two- to threefold higher risk of suffering an acute myocardial infarction compared to individuals without the disease, and have a poorer post-infarction prognosis. Part of this vulnerability is due to both structural and functional alterations in the diabetic heart, known as diabetic cardiomyopathy. This condition is characterized by increased interstitial fibrosis at the cardiac level, persistent inflammation, and a poorer adaptation to ischemic stress.
Although various cardioprotective strategies have shown efficacy in experimental settings, the same benefits have not been replicated clinically. “This failure is partly attributed to the presence of comorbidities, which alter endogenous cardioprotective signaling pathways. Hence, the need to seek new strategies capable of protecting the heart against infarction in the presence of diabetes,” says Sebastià Alcover, first author of the article.
The study published in Diabetes uses a preclinical model that develops a diabetic cardiomyopathy phenotype with high similarity to the human condition, characterized by ventricular dysfunction and interstitial fibrosis.
In these animals with diabetic cardiomyopathy, acute myocardial infarction was induced by transient ligation (45 minutes) of the left anterior descending coronary artery, followed by 24 hours of reperfusion. Atorvastatin was administered to a group of animals intravenously and early after infarct induction, while another group received a vehicle. Additionally, for comparative purposes, two groups of normoglycaemic control animals (one treated and one untreated) were included.
“Intravenous atorvastatin treatment significantly reduced the infarction-induced cardiac damage in animals with diabetic cardiomyopathy compared to those that received the vehicle, achieving a benefit similar to that observed in the treated normoglycaemic animals. Moreover, this benefit was accompanied by better preservation of cardiac function,” adds Dr. Vilahur.
According to Sebastià Alcover, “The observed benefits are not due to atorvastatin’s ability to lower circulating lipids, but rather to its capacity to inhibit the synthesis of isoprenoid intermediates by blocking the HMG-CoA reductase enzyme.” This inhibition leads to greater activation of the AMPK protein (a key enzyme in cardiac metabolism that is reduced in the presence of diabetes), reduced apoptotic cell death and inflammatory infiltration, as well as improved reparative fibrosis in the infarcted heart.
Although this is an experimental study, the authors emphasize the importance of these preclinical results. “The possibility of having a drug that is widely used in clinical practice and capable of reducing cardiac damage in the presence of diabetic cardiomyopathy or other cardiovascular risk factors—as already shown previously by Dr. Vilahur’s group—deserves to be investigated in diabetic patients,” concludes Sebastià Alcover.
Alcover S, López S, Ramos L, Muñoz-García N, Gallinat A, Suades R, Badimon L, Vilahur G. Cardioprotection during myocardial infarction in diabetic cardiomyopathy. Diabetes 2025. https://doi.org/10.2337/db24-0510.
