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Intensive LDL Lowering After MI

Insights from the IDEAL trial about ideal LDL targets after myocardial infarction

Several recent statin trials have compared outcomes with intensive versus standard LDL-lowering strategies (Journal Watch Cardiology Apr 16 2004, Oct 29 2004, and Apr 22 2005). Now, in a randomized, open-label trial with blinded endpoint evaluation, researchers compared high-dose atorvastatin (80 mg/day) with standard-dose simvastatin (20 mg/day) in 8888 patients (mean age, 62; maximum age, 80; 81% men) with histories of MI. Subjects were recruited at 190 centers in northern Europe and followed for a median of 4.8 years. The trial, Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL), was funded by the manufacturer of atorvastatin.

Among patients who were not using statins at randomization, mean LDL levels dropped by 49% (to 81 mg/dL) with atorvastatin after 12 weeks and by 33% (to 104 mg/dL) with simvastatin. In the overall cohort, 5-year incidence of the primary composite endpoint (coronary death, nonfatal MI, or cardiac arrest with resuscitation) did not differ significantly between the atorvastatin group (9.3%) and the simvastatin group (10.4%), nor did any mortality endpoint. However, incidence of a secondary composite endpoint (the primary endpoint plus stroke) was significantly lower with atorvastatin (12.0%) than with simvastatin (13.7%). The authors note an overall advantage of intensive LDL-lowering with atorvastatin: 68 first cardiovascular events prevented (95% CI, 39–97 events) per 1000 patients over 5 years.

Adverse events resulting in permanent drug discontinuation were significantly more common with atorvastatin than with simvastatin (9.6% vs. 4.2%), as were liver-enzyme elevations (2 consecutive ALT readings >3x the upper limit of normal, 0.97% vs. 0.11%). Serious myopathy and rhabdomyolysis were rare in both groups.

Comment: In these subjects with histories of MI, an intensive LDL-lowering strategy with atorvastatin did not show an advantage over standard LDL lowering for preventing a primary-endpoint event, but a significant advantage was evident when stroke was added to the endpoint. On its own, this finding would not be definitive. However, a growing number of studies have shown an incremental benefit of using statins to lower LDL levels below current guideline targets. The present findings marginally strengthen that evidence base.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology December 9, 2005

Citation(s):

Pedersen TR et al. for the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) Study Group. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction. The IDEAL study: A randomized controlled trial. JAMA 2005 Nov 16; 294:2437-45.

• Original article (Subscription may be required)
• Medline abstract (Free)

Cannon CP. The IDEAL cholesterol: Lower is better. JAMA 2005 Nov 16; 294:2492-4.

• Original article (Subscription may be required)
• Medline abstract (Free)

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