Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease

TLDR

Lowering LDL cholesterol below current targets has been shown to benefit patients with acute coronary syndromes. This study prospectively evaluated the efficacy and safety of reducing LDL cholesterol to <100 mg/dL in stable CHD patients by comparing 10 mg versus 80 mg atorvastatin daily. In a double‑blind randomized trial of 10,001 stable CHD patients, participants were followed for a median 4.9 years, with the primary endpoint being a first major cardiovascular event; mean LDL levels were 77 mg/dL with 80 mg atorvastatin and 101 mg/dL with 10 mg. Intensive 80 mg atorvastatin therapy reduced major cardiovascular events by 22 % relative (2.2 % absolute) versus 10 mg, with a higher but low incidence of liver aminotransferase elevations (1.2 % vs 0.2 %) and no difference in overall mortality.

Abstract

Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD).A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke.The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality.Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.