Background: Beyond lipid-lowering, statins exert cardioprotective effects. High-dose statin treatment seems to reduce cardiovascular complications in high-risk patients. The ideal timing and administration regime remain unknown.
Objectives: This study compared the cardioprotective effects of intravenous statin administration during myocardial infarction (MI) with oral administration immediately post-MI.
Methods: Hypercholesterolemic pigs underwent MI induction (90 min of ischemia) and were kept for 42 days. Animals were distributed in 3 arms (A): A1 received an intravenous bolus of atorvastatin during MI; A2 received an intravenous bolus of vehicle during MI; and A3 received oral atorvastatin within 2 h post-MI. A1 and A3 remained on daily oral atorvastatin for the following 42 days. Cardiac magnetic resonance analysis (days 3 and 42 post-MI) and molecular/histological studies were performed.
Results: At day 3, A1 showed a 10% reduction in infarct size compared with A3 and A2 and a 50% increase in myocardial salvage. At day 42, both A1 and A3 showed a significant decrease in scar size versus A2; however, A1 showed a further 24% reduction versus A3. Functional analyses revealed improved systolic performance in A1 compared with A2 and less wall motion abnormalities in the jeopardized myocardium versus both groups at day 42. A1 showed enhanced collagen content and AMP-activated protein kinase activation in the scar, increased vessel density in the penumbra, higher tumor necrosis factor α plasma levels and lower peripheral blood mononuclear cell activation versus both groups.
Conclusions: Intravenous administration of atorvastatin during MI limits cardiac damage, improves cardiac function, and mitigates remodeling to a larger extent than when administered orally shortly after reperfusion. This therapeutic approach deserves to be investigated in ST-segment elevation MI patients.
Keywords: cardioprotection; myocardial infarction; pigs; statin; timing.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
HMG-CoA reductase inhibition prior reperfusion improves reparative fibrosis post-myocardial infarction in a preclinical experimental model.Int J Cardiol. 2014 Aug 20;175(3):528-38. doi: 10.1016/j.ijcard.2014.06.040. Epub 2014 Jul 2. Int J Cardiol. 2014. PMID: 25023790
Protective Effects of Ticagrelor on Myocardial Injury After Infarction.Circulation. 2016 Nov 29;134(22):1708-1719. doi: 10.1161/CIRCULATIONAHA.116.024014. Epub 2016 Oct 27. Circulation. 2016. PMID: 27789556
Molecular pathways involved in the cardioprotective effects of intravenous statin administration during ischemia.Basic Res Cardiol. 2019 Nov 28;115(1):2. doi: 10.1007/s00395-019-0760-z. Basic Res Cardiol. 2019. PMID: 31781960
Atorvastatin efficacy in the primary and secondary prevention of cardiovascular events.Drugs. 2007;67 Suppl 1:29-42. doi: 10.2165/00003495-200767001-00004. Drugs. 2007. PMID: 17910519 Review.
Myocardial Infarct Size by CMR in Clinical Cardioprotection Studies: Insights From Randomized Controlled Trials.JACC Cardiovasc Imaging. 2017 Mar;10(3):230-240. doi: 10.1016/j.jcmg.2017.01.008. JACC Cardiovasc Imaging. 2017. PMID: 28279370 Free PMC article. Review.