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High intensity statin4/1/2023 ![]() Patients were randomized to receive either loading doses of 80 mg atorvastatin (n=2,087) or placebo (n=2,104) between 2 to 12 hours before PCI and next day, and were to receive 40 mg atorvastatin for 30 days afterward. The investigators sought to test an interesting hypothesis whether high dose atorvastatin before invasive management may reduce adverse cardiac events in ACS. Recently published study, the SECURE-PCI (Statins Evaluation in Coronary Procedures and Revascularization) trial was designed to assess the effect of periprocedural administration of statin in patients with ACS and planned coronary revascularization ( 13). However, it had not been revealed whether initiation of statin before PCI or very early phase after event onset may be beneficial or harmful in patients with ACS. Study protocol of the trials seem to be pragmatic that majority of patients with ACS may be considered for invasive management and that there was no reason to avoid statin initiation for stabilized patients after PCI in clinical practice. The studies tested in-hospital initiation of statin defined by the study protocol and demonstrated meaningful results in favor of more potent lipid lowering treatment. In both PROVE-IT and IMPROVE-IT trials including nearly 70% of patients undergoing PCI for treatment of index event, subjects were allowed to be enrolled within 10 days after onset of ACS events and before discharge. The MIRACL trial allowed randomization between 1 and 3 days after admission, however, it only included patients with non-ST elevation ACS not planning to undergo coronary revascularization. Previous trials assessing early lipid lowering strategies enrolled patients during in-hospital period after index ACS event. More importantly, definite evidences supporting administration of statin at very early phase of ACS or before invasive management are limited. There have been also concerns about safety of high intensity statin administration during early (or unstable) phase of ACS. Current US and European guidelines have emphasized the importance of intensive lipid lowering, which is one of cornerstones for management of atherosclerotic coronary artery disease especially in high risk patients, with using high intensity statin or achieving very low LDL-C concentration ( 8- 12).Ĭoncept of early initiation of statin has been accepted as a manner of starting statin treatment in a patient with stable condition before discharge after index ACS event ( 8, 10). Simvastatin-ezetimibe combination was more effective in reducing average LDL-C level than simvastatin monotherapy and it resulted in lower incidences of primary end point during 7-year follow-up. The IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study compared simvastatin plus additional ezetimibe with simvastatin monotherapy ( 7). Compared with moderate intensity, 40 mg pravastatin, 80 mg atorvastatin achieved lower density lipoprotein cholesterol (LDL-C) in patients hospitalized for ACS, which brought favorable clinical outcomes with 16% reduction in major cardiovascular events for 2 years in the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) study ( 6). 17.4%, relative risk 0.84, P =0.048) including death, myocardial infarction, cardiac arrest with resuscitation, and recurrent ischemic symptom within 16 weeks in patients with ACS ( 5). In the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) study, administration of 80 mg atorvastatin within 24 to 96 hours of hospital, compared with placebo, reduced the incidence of cardiovascular events (14.8% vs. The other mechanisms including inhibition of inflammatory activity, reduction of lipid accumulation in the plaque, and improving endothelial function have been also suggested as statin effects ( 4). Previous studies explored favorable mechanisms of early initiation of statin with plaque modification by reduction of necrotic core in plaques with high risk morphology ( 2), or in plaques with ACS ( 3). Cholesterol-independent, pleiotropic effects of statin have been widely investigated with regard to suppression of plaque vulnerability ( 1). ![]() Benefit of early initiation of intensive lipid lowering treatment is established in patients with acute coronary syndrome (ACS). ![]()
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