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Am Fam Physician. 2005;71(3):578-580

The beneficial effects of statin medications in decreasing cardiovascular disease are well established. Current guidelines suggest titrating statin therapy to achieve a low-density lipoprotein (LDL) cholesterol level below 100 mg per dL (2.59 mmol per L) in patients with established coronary heart disease or diabetes. Cannon and colleagues designed a trial to determine if lowering LDL levels even further would provide additional benefits in patients with acute coronary syndromes.

This multinational study enrolled 4,162 patients, of whom 22 percent were women, and less than 10 percent were from minority ethnic groups. Patients were recruited who had an acute coronary syndrome (myocardial infarction or unstable angina) within the previous 10 days. The trial targeted patients who had a total cholesterol of 240 mg per dL (6.21 mmol per L) or less in those not taking lipid-lowering medications, or of 200 mg per dL (5.17 mmol per L) or less if already taking such medications. Patients received standard medical and interventional treatment for acute coronary syndrome. Subsequent lipid-lowering therapy was randomized to either standard treatment (pravastatin, 40 mg daily) or intensive treatment (atorvastatin, 80 mg daily). Patients were followed for any cardiovascular event (death, myocardial infarction, hospitalization for unstable angina, or subsequent revascularization) over a mean duration of two years. The mean LDL level was 106 mg per dL (2.74 mmol per L) in both treatment groups before treatment. The group receiving standard treatment had a decrease in LDL levels to an average of 95 mg per dL (2.46 mmol per L) , while those on intensive therapy dropped to an average of 62 mg per dL (1.60 mmol per L). High-density lipoprotein increased by 8.1 percent in the pravastatin group and by 6.5 percent among those taking atorvastatin.

Recurrence of a cardiovascular event during follow-up occurred less often in those on intensive treatment (22.4 percent) than in those receiving standard lipid-lowering therapy (26.3 percent). The decreased incidence of cardiovascular events with more intensive treatment started within the first month of the study and persisted over the two years of follow-up. Of the components that were combined into the primary end point of any cardiovascular event, statistically significant reductions were noted for revascularization and unstable angina, while the rates of death, myocardial infarction, and stroke were not significantly changed. The benefits of intensive treatment were similar in men, women, and patients with diabetes. Those who began the study with an LDL level below 125 mg per dL (3.23 mmol per L) had a lesser reduction in cardiovascular events than those who began above that level.

The authors conclude that intensive lipid-lowering treatment after an acute coronary syndrome significantly reduces median LDL cholesterol levels and provides greater protection against death or cardiovascular events than standard regimens. The authors note that a head-to-head trial of the same statin at different dosages would be a logical next step.

editor's note: A similar trial was recently reported1 that also compared 40 mg of pravastatin with 80 mg of atorvastatin daily in patients with known coronary heart disease. Patients underwent intravascular ultrasound examination of coronary artery lesions before and after 18 months of randomized statin treatment. Those receiving more intense lipid treatment (average LDL cholesterol level of 79 mg per dL [2.05 mmol per L]) had less progression of atheroma volume compared with those receiving lower dose statin therapy. Although neither of these trials showed robust benefits from higher intensity lipid-lowering treatment, they are consistent. Lowering LDL levels even further than the usual goal of 100 mg per dL (2.59 mmol per L) in those with coronary heart disease is likely to be feasible with only modest increases in effort and expense and has at least preliminary data to show it is beneficial. —b.z.

REFERENCENissenSETuzcuEMSchoenhagenPBrownBGGanzPVogelRAet alEffect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis. A randomized controlled trial.JAMA2004;291:1071–80.

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