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Lipid-Lowering After Acute Coronary Syndromes -- Intensive Is Better

Intensive statin therapy reduces adverse events after ACS -- but is it really lipid lowering, or some other effect of statins?

Current guidelines suggest that patients with coronary artery disease be treated to achieve LDL cholesterol levels of <100 mg/dL. New data from two studies, one sponsored by the maker of pravastatin and one sponsored by the maker of atorvastatin, suggest that intensive lipid-lowering after acute coronary syndrome (ACS) is associated with better outcomes than is moderate lowering.

Cleveland Clinic researchers reported on a double-blind multicenter trial (called REVERSAL) of 654 patients who required angiography and had luminal narrowing of 20% in at least one vessel; patients were randomized to daily pravastatin (40 mg) or atorvastatin (80 mg). Baseline LDL levels (mean, 150 mg/dL) were reduced to 110 mg/dL in the pravastatin group and to 79 mg/dL in the atorvastatin group; C-reactive protein (CRP) levels (mean, 2.9 mg/L) were reduced by 5.2% and 36.4%, respectively. Atheroma progression, as measured with intravascular ultrasound, was significantly less in the atorvastatin group than in the pravastatin group after 18 months.

In a second study (called PROVE-IT), investigators randomized 4162 patients who had been hospitalized for ACS within the past 10 days to the same statins and doses as those used in REVERSAL. At 24 months, median LDL levels were 95 mg/dL in the pravastatin group and 62 mg/dL in the atorvastatin group; CRP levels (baseline mean, 12.3 mg/L) fell by 83% and 89%, respectively. Significantly more pravastatin patients than atorvastatin patients (26.3% vs. 22.4%) experienced the primary combined endpoint (death, myocardial infarction, unstable angina requiring rehospitalization, revascularization at 30 days after randomization, and stroke).

Comment: The results of these studies, one with an imaging endpoint and one focused on patient outcomes, provide strong evidence that intensive lipid-lowering regimens can reduce atherosclerosis progression and can decrease adverse events after admission for ACS. What is not as clear is why: Is it really the decrease in LDL levels, or do statins differ in other effects, such as reduction in inflammation or stabilization of endothelium? The degree of reduction in adverse events in the PROVE-IT study is consistent with the degree of LDL lowering; however, in REVERSAL, the degree of reduction in plaque progression was larger than would be expected due to LDL lowering alone. Because both studies involved two different statins, and the atorvastatin dosage was expected to yield lower LDL levels, we'll need additional data to answer these questions. Nonetheless, an editorialist predicts a major change in our approach to lipid management -- aggressive therapy toward LDL levels well below current guidelines of 100 mg/dL for patients with coronary disease.

— Kirsten E. Fleischmann, MD, MPH

Published in Journal Watch General Medicine April 13, 2004

Citation(s):

Nissen SE et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: A randomized controlled trial. JAMA 2004 Mar 3; 291:1071-80.

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• Medline abstract (Free)

Cannon CP et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004 Apr 8; 350:1495-504.

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Topol EJ. Intensive statin therapy -- A sea change in cardiovascular prevention. N Engl J Med 2004 Apr 8; 350:1562-4.

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• Medline abstract (Free)