A study published in the European Heart Journal found that intravenous atorvastatin administered during a myocardial infarction reduces cardiac muscle damage more effectively than an oral loading dose given before the event. The study was led by researchers at the Institut de Recerca Sant Pau.
Researchers conducted the study using a hypercholesterolemic pig model that reproduces cardiovascular disease conditions observed in humans. The experiment compared administering an oral loading dose two hours before inducing a myocardial infarction with administering an intravenous formulation 15 minutes after the onset of ischemia. Researchers induced myocardial infarction in the animal subjects through controlled balloon occlusion of a coronary artery followed by revascularization.
Gemma Vilahur, Head of the Molecular Pathology and Therapeutics of Atherothrombotic and Ischemic Diseases Group at IR Sant Pau and Group Leader at CIBERCV, said, "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." Cardiac damage was evaluated using cardiac magnetic resonance imaging on day 3 and day 42 after the procedure.
Intravenous atorvastatin administration reduced infarct size by 20 percent and cardiac edema by 13 percent compared to the oral loading dose three days after the event. Forty-two days after the event, animals receiving intravenous treatment exhibited a 20 percent smaller scar size, improved preservation of left ventricular ejection fraction, and reduced end-systolic volume compared to the oral treatment group. The study recorded no relevant differences in the no-reflow phenomenon between the two treatment groups during the initial days following infarction.
Sergi Otero, a PhD candidate and first author of the study, said, "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." Otero said, "The key is that we are intervening at the moment the injury occurs, not afterward." He added, "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."
The intravenous atorvastatin formulation used in the study was developed and patented by the institute. The development of the patented intravenous formulation resulted in the creation of a spin-off company named Ivestatin Therapeutics S.L. Intravenously administered atorvastatin reduces cardiomyocyte death, attenuates inflammatory responses, and activates AMP-activated protein kinase. Vilahur said, "These results indicate that the timing and route of administration are key determinants of treatment efficacy."