Reducing the damage sustained by the heart during a myocardial infarction remains one of the major challenges in cardiology, even when the blocked coronary artery is reopened in a timely manner. Part of the myocardial injury continues to be difficult to prevent despite advances in reperfusion therapies. In the search for solutions 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 cardiac protection compared with administration of a pre-infarction oral loading dose.
Although clinical guidelines recommend the early use of statins after myocardial infarction, uncertainty remains regarding their impact when administered at earlier stages and, especially, 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 damage .
“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 reducing cardiac damage than administration of a pre-infarction oral loading dose,” explains Gemma Vilahur, PhD , Head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Group at IR Sant Pau and Group Leader at the Biomedical Research Networking Center for Cardiovascular Diseases (CIBERCV, CB16/11/00411) , and 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 allows controlled analysis of myocardial damage associated with infarction . The animals received oral atorvastatin treatment during the days preceding myocardial infarction to reproduce the clinical scenario of patients already receiving these lipid-lowering therapies.
Building on this model, the researchers compared two administration strategies at the time of the acute event: a pre-infarction oral loading dose and intravenous administration during the ischemic episode itself , a formulation developed within the IR Sant Pau environment that has been patented and led to the creation of a spin-off company (Ivestatin Therapeutics S.L.). Specifically, the oral loading dose was administered 2 hours before 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 occlusion of a coronary artery followed by revascularization, simulating the process that occurs in patients. Cardiac damage was assessed using serial cardiac magnetic resonance imaging (MRI) a few days after the event (Day 3) and again several weeks later (Day 42). Cardiac MRI is a reference imaging technique for tissue characterization and infarct size quantification. This two-time-point follow-up provided a precise measure of injury and its evolution over time.
“Working with a model that closely reproduces what occurs in patients and combining it with advanced cardiac imaging techniques allowed us to evaluate how the timing and route of treatment administration influence cardiac damage,” explains Sergi Otero , PhD candidate, researcher in the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Group, and first author of the study. “This design gave us the opportunity to analyze not only the initial injury but also the subsequent evolution of the heart after myocardial infarction .”
Less Initial Damage and Improved Cardiac Recovery
The results indicated that intravenous administration during myocardial infarction was associated with a significant reduction in myocardial damage during the acute phase (Day 3 after the event) , including lower necrosis—meaning less cardiac tissue death—and less edema associated with cardiac inflammation, compared with the oral loading dose 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 injury to the cardiac muscle at the time the infarction occurs.
This initial difference persisted over time. At Day 42, animals treated with the intravenous formulation showed a smaller scar size (20% lower) and better preservation of left ventricular ejection fraction , along with a reduction in end-systolic volume, an indicator of improved cardiac contractile and pumping capacity, compared with the oral administration strategy. The study found no relevant differences in the no-reflow phenomenon—that is, lack of tissue perfusion despite successful reopening of the artery—during the first days after infarction. This suggests that the benefit of intravenous treatment is not related 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 . “That makes it possible to reduce the initial damage and generates a cascade 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 .
Acting at the Critical Moment to Protect the Heart
Statins are part of the standard treatment after myocardial infarction, and, in certain settings, loading doses are administered before coronary interventions. However, pre-event administration has limitations because acute myocardial infarction typically occurs unpredictably, making it impossible in numerous instances to anticipate the timing of the event. In this scenario, the intravenous route enables immediate action during a critical phase, when cardiac tissue is undergoing ischemic injury and remains potentially salvageable. The ability to modulate damage from its earliest stages not only has an immediate impact but also directly influences the process of cardiac remodeling and the heart’s capacity for medium-term recovery, 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 help limit the extent of injury and preserve the viability of cardiac tissue 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 to protect the heart during a phase in which therapeutic options have so far been limited.”
Overall, 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 the acute event. Future evaluation in clinical studies will be essential to determine its impact on patients and its potential incorporation into clinical practice.
European Heart Journal
Experimental study
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