Context: Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol(LDL-C)than is commonly applied clinically will provide further benefit in stable coronary artery disease. Objective: To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction(MI). Design, Setting, and Participan ts: The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist prac tices in northern Europe between March 1999 and March 2005 with a median follow -up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Interventions: Patients were randomly assigned to receive a high dose of atorvastatin(80 mg/d; n=4439), or usual-dose simvastatin(20 mg/d; n=4449). Main Outcome Measure: Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitati on. Results: During treatment, mean LDL-C levels were 104(SE, 0.3)mg/dL in the simvastatin group and 81(SE, 0.3)mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients(10.4%)and in 411 atorvastatin patients(9.3%)(hazard ratio[HR], 0.89; 95%CI, 0.78-1.01; P=.07). Nonfatal acute MI occurred in 321(7.2%)and 267(6.0%)in the 2 groups(HR, 0.83; 95%CI, 0.71-0.98; P=.02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively(HR, 0.87; 95%CI, 0.77-0.98; P=.02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients(HR, 0.84; 95%CI, 0.76-0.91; P< .001). Noncardiovascular death occurred in 156(3.5%)and 143(3.2%)in the 2 groups(HR, 0.92; 95%CI, 0.73-1.15; P=.47). Death from any cause occurred in 374(8.4%)in the simvastatin group and 366(8.2%)in the atorvastatin group(HR, 0.98; 95%CI, 0.85-1.13; P=.81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43(1.0%)vs 5(0.1%)withdrawals(P< .001). Serious myopathy and rhabdomyolysis were rare in both groups. Conclusions: In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute M I. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in no ncardiovascular mortality or other serious adverse reactions. Trial Registration : ClinicalTrials.gov Identifier: NCT00159835. Context: Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. Objective: To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). Design, Setting, and Participan ts: The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist prac tices in northern Europe between March 1999 and March 2005 with a median follow -up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Interventions: Patients were randomly assigned to receive a high dose of atorvastatin (80 n = 4439), or usual-dose simvastatin (20 mg / d; n = 4449). Main Outcome Measure: Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, Results: During treatment, mean LDL-C levels were 104 (SE, 0.3) mg / dL in the simvastatin group and 81 (SE, 0.3) mg / dL in the atorvastatin group. occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 ) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02) but no differences were seen in the other components of the primary end point. Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.77-0.98; P = .02) CI, 0.76-0.91; P <.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any of the causes occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P <. 001). Serious myopathy and rhabdomyolysis were rare in both groups. Conclusions: In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute M I. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in no ncardiovascular mortality or other serious adverse reactions. Trial Registration: ClinicalTrials.gov Identifier: NCT00159835.