Effect of Intensive Lipid Lowering on Progression of Coronary Atherosclerosis: Evidence for an Early Benefit from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Trial

Statins reduce both atherogenic lipoproteins and high-sensitivity C-reactive protein (hsCRP). The optimal strategy for administration of lipid-lowering agents has evolved considerably during the past 2 years. Several studies have compared the effects of intensive versus moderate lipid lowering in secondary prevention of coronary events. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was a double-blind, randomized trial comparing the effect that 2 different statins, administered for 18 months, had on atherosclerotic burden measured by intravascular ultrasound (IVUS). At 34 centers in the United States, 654 patients were randomized to moderate lipid lowering using pravastatin 40 mg or intensive treatment with atorvastatin 80 mg. IVUS was performed during baseline catheterization and repeated after 18 months of treatment. Efficacy parameters included changes in atheroma burden determined by IVUS, lipoprotein levels, and CRP levels. Baseline low-density lipoprotein (LDL) cholesterol (mean, 3.9 mmol/L [150.2 mg/dL]) levels were reduced to 2.8 mmol/L (110 mg/dL) in the pravastatin 40-mg group compared with 2.0 mmol/L (79 mg/dL) in the atorvastatin 80-mg arm (p <0.0001). CRP decreased 5.2% with pravastatin and 36.4% with atorvastatin (p <0.0001). Changes in atheroma burden showed a significantly lower progression rate in the intensive arm for all 3 prespecified IVUS efficacy measures. For all IVUS end points, progression occurred in the moderate-treatment cohort. However, plaque volume was unchanged in the intensive arm, indicating absence of progression. Post hoc analyses demonstrated that greater reductions in both lipid levels and hsCRP were associated with slower disease progression. The slowest progression occurred in patients with above-median reductions in both LDL cholesterol and CRP. For patients with coronary artery disease, intensive treatment with atorvastatin 80 mg reduced progression of coronary atherosclerosis compared with a more moderate regimen consisting of pravastatin 40 mg. Compared with baseline, intensively treated patients had no change in atheroma burden, whereas moderately treated patients showed progression. These differences are related to the greater reduction in atherogenic lipoproteins and CRP in intensively treated patients.