Timing of high intensity statin for acute coronary syndrome: how earlier initiation makes better?

Benefit of early initiation of intensive lipid lowering treatment is established in patients with acute coronary syndrome (ACS). Cholesterol-independent, pleiotropic effects of statin have been widely investigated with regard to suppression of plaque vulnerability (1). 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). 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). 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. 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). 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). The IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study compared simvastatin plus additional ezetimibe with simvastatin monotherapy (7). 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 [32.7% vs. 34.7%, hazard ratio (HR) 0.94, P=0.016] during 7-year follow-up. 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)