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The IDEAL Study: A Randomized Controlled Trial

Terje R. Pedersen, MD, PhD; Ole Faergeman, MD, DMSc; John J. P. Kastelein, MD, PhD; Anders G. Olsson, MD, PhD; Matti J. Tikkanen, MD, PhD; Ingar Holme, PhD; Mogens Lytken Larsen, MD, DMSc; Fredrik S. Bendiksen, MD; Christina Lindahl, MD; Michael Szarek, MS; John Tsai, MD; for the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group

JAMA. 2005;294:2437-2445.

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 Participants  The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices 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 resuscitation.

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 MI. 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 noncardiovascular mortality or other serious adverse reactions.

Trial Registration  ClinicalTrials.gov Identifier: NCT00159835.

Author Affiliations: Centre for Preventive Medicine, Ullevål University Hospital, Oslo, Norway (Drs Pedersen and Holme); Department of Medicine–Cardiology A, Århus University Hospital, Århus, Denmark (Drs Faergeman and Larsen); Academic Hospital Amsterdam, Amsterdam, the Netherlands (Dr Kastelein); Department of Internal Medicine, University Hospital, Linköping, Sweden (Dr Olsson); Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (Dr Tikkanen); Pfizer Sweden, Täby, Sweden (Dr Lindahl); and Pfizer Inc, New York, NY (Mr Szarek and Dr Tsai). Dr Bendiksen is in private practice in Hamar, Norway.

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