Pretreatment with statins may reduce cardiovascular morbidity and mortality after elective surgery and percutaneous coronary intervention: Clinical evidence and possible underlying mechanisms

Ramanna Merla, Iyad N. Daher, Yumei Ye, Barry F. Uretsky, Yochai Birnbaum

Research output: Contribution to journalReview article

32 Scopus citations

Abstract

After Murry et al (Circulation 1986;74:1124) described ischemic preconditioning in 1986, numerous pharmacologic agents with effects simulating ischemic preconditioning have been identified. With the exception of β-blockers, most such agents have no proven clinical benefit in the setting of myocardial ischemia. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been consistently demonstrated to reduce myocardial injury, morbidity, and mortality in the clinical setting, both perioperatively and after percutaneous coronary intervention. Although the precise mechanism underlying their additional protective effect is not yet fully understood, it appears to be immediate in action and independent of cholesterol lowering. Experimental data from several animal models of ischemia and reperfusion have demonstrated an infarct size reduction with prior statin administration. At the cellular level, statins activate the phosphoinositol-3 kinase and Akt signaling cascade. Statins also increase expression and activity of endothelial nitric oxide synthase, inducible nitric oxide synthase, ecto-5′-nucleotidase, cyclooxygenase-2, and other prostaglandin synthesis pathway enzymes. However, when given by oral route to animals, relatively high dose of statins is needed to exert maximal protective effect. Understanding the underlying mechanism may enable to maximize the protective effect by using drug combination with synergistic activity and to avoid medications that may interfere with the protective effect of statins (ie, selective and nonselective cyclooxygenase-2 inhibition). Future clinical applications include preoperative and periprocedural risk reduction.

Original languageEnglish (US)
Pages (from-to)391-402
Number of pages12
JournalAmerican Heart Journal
Volume154
Issue number2
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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