Reducing the damage sustained by the heart during a myocardial infarction remains one of the major challenges in cardiology, even when the coronary artery can be reopened in time. Part of the myocardial injury remains difficult to prevent despite advances in reperfusion. In the search for strategies to limit this damage, a study led by the Institut de Recerca Sant Pau (IR Sant Pau), published in the European Heart Journal, shows that intravenous administration of atorvastatin during the ischemic event itself may improve cardioprotection compared with the administration of an oral loading dose before myocardial infarction.
Although clinical guidelines recommend the early use of statins after myocardial infarction, questions remain regarding their impact when administered at earlier stages and, particularly, during the ischemic episode itself. This uncertainty also extends to the timing and route of administration, factors that may influence their ability to limit myocardial injury.
“The main contribution of this study is demonstrating for the first time that intravenous administration of atorvastatin during the ischemic event itself has a significantly greater impact on cardiac injury than the administration of an oral loading dose before myocardial infarction,” explains Dr. Gemma Vilahur, head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Research Group at IR Sant Pau and group leader at the Biomedical Research Networking Center for Cardiovascular Diseases (CIBERCV, CB16/11/00411), corresponding author of the study.
A Highly Translational Model That Reproduces What Happens in Patients
The study was conducted in a hypercholesterolemic pig model, which reproduces conditions commonly observed in patients with cardiovascular disease and enables controlled analysis of cardiac injury associated with myocardial infarction. The animals received oral atorvastatin treatment during the days preceding myocardial infarction, with the aim of reproducing the clinical setting of patients who are already receiving these lipid-lowering drugs.
On this basis, the investigators compared two administration strategies at the time of the acute event: an oral loading dose before myocardial infarction and intravenous administration during the ischemic episode itself, a formulation developed within the IR Sant Pau environment and the subject of a patent and the creation of a spin-off company (Ivestatin Therapeutics S.L.). Specifically, the oral loading dose was administered 2 hours before myocardial infarction induction, whereas the intravenous formulation was administered 15 minutes after the onset of the ischemic episode. Myocardial infarction was induced in a controlled manner through balloon angioplasty occlusion of a coronary artery followed by revascularization, making it possible to simulate the process that occurs in patients. Cardiac injury was assessed by serial cardiac magnetic resonance imaging (MRI) a few days after the event (Day 3) and again several weeks later (Day 42). Cardiac MRI is the reference imaging technique for tissue characterization and infarct size quantification. This follow-up at two different time points enabled a precise measurement of the injury and its progression over time.
“Working with a model that closely reproduces what happens in patients and combining it with cardiac imaging techniques has allowed us to evaluate how the timing and route of treatment administration influence cardiac injury,” explains Sergi Otero, PhD student, researcher in the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Research Group, and first author of the study. “This design gave us the opportunity to analyze not only the initial injury but also the evolution of the heart after myocardial infarction.”
The results indicated that intravenous administration during myocardial infarction was associated with a significant reduction in myocardial injury during the acute phase (Day 3 after the event), with less necrosis, meaning less cardiac tissue death, and less edema associated with cardiac inflammation, compared with the oral preloading strategy. Specifically, intravenous atorvastatin administration reduced infarct size by 20% and edema by 13% compared with the oral loading dose. These parameters, assessed by MRI, reflect less damage to the heart muscle at the time myocardial infarction occurs.
This initial difference was maintained over time. At Day 42, animals treated with the intravenous formulation showed a smaller scar burden (20% lower) and better preservation of left ventricular ejection fraction, together with a reduction in end-systolic volume, an indicator of improved cardiac contraction and pumping capacity, compared with oral preloading. The study showed no relevant differences in the no-reflow phenomenon, that is, the lack of tissue perfusion despite successful reopening of the artery, during the first days after myocardial infarction. This suggests that the benefit of intravenous treatment is not due to changes in the microvascular circulation but rather to a direct effect on myocardial injury during the ischemic phase.
“The key is that we are intervening at the moment the injury occurs, not afterward,” explains Sergi Otero. “This makes it possible to reduce the initial damage and has a cascading effect on the subsequent evolution of the heart, both structurally and functionally.” These findings reinforce the importance of intervening as early as possible during the ischemic event itself.
Statins are part of the standard treatment after myocardial infarction, and, in certain settings, loading doses are used before coronary interventions. However, pre-event administration has limitations because acute myocardial infarction usually occurs unpredictably, and it is not always possible to anticipate when the event will occur. In this scenario, the intravenous route allows immediate action during a critical phase, when cardiac tissue is undergoing ischemic injury and remains potentially salvageable. The possibility of modulating damage from its earliest stages not only has an immediate impact but also directly influences the process of cardiac remodeling and the heart’s ability to recover in the medium term, a key factor in patients’ clinical outcomes after myocardial infarction and in the subsequent development of heart failure.
Beyond its lipid-lowering effect, that is, its ability to reduce blood cholesterol levels, the authors demonstrated that intravenously administered atorvastatin acts almost immediately on several mechanisms involved in myocardial injury. These include reducing cardiomyocyte death, attenuating the inflammatory response, and activating AMP-activated protein kinase (AMPK), a key regulator of cellular energy metabolism. These effects contribute to limiting the extent of injury and preserving cardiac tissue viability during myocardial infarction.
“These results indicate that the timing and route of administration are key determinants of treatment efficacy,” says Dr. Gemma Vilahur. “Being able to act directly during the event opens a new avenue for protecting the heart during a phase in which therapeutic options have so far been limited.”
Taken together, the findings reinforce the importance of early intervention during myocardial infarction and point to the potential of intravenous statin administration as a complementary strategy in the management of acute events. Future evaluation in clinical studies will be essential to determine its impact in patients and its possible incorporation into clinical practice.
Otero S, Radike M, Ben-Aicha S, Mendieta G, Gutiérrez M, Sutelman P, Borrell-Pagès M, Hidalgo A, Badimon L, Vilahur G. Cardioprotection with Intravenous Statin Administration During Myocardial Infarction vs. Oral Preloading: A Preclinical Study. Eur Heart J. 2026. https://doi.org/10.1093/eurheartj/ehag269.
