Reversing Atherosclerosis With Aggressive Lipid Lowering - REVERSAL
The goal of the trial was to evaluate the effect of treatment with an aggressive lipid-lowering strategy with atorvastatin versus a moderate lipid-lowering strategy with pravastatin on coronary atherosclerosis progression assessed using intravascular ultrasound (IVUS) in patients with symptomatic coronary artery disease (CAD) and elevated LDL.
Treatment with an aggressive lipid-lowering strategy with atorvastatin will be associated with a reduction in coronary atherosclerosis progression compared with a moderate lipid-lowering strategy with pravastatin in patients with symptomatic CAD.
Patients Enrolled: 502
Mean Follow Up: 18 months
Mean Patient Age: Mean age 56 years
Symptomatic CAD, coronary angiography with >20% stenosis, and LDL 125-210 mg/dl after eight-week washout
Percent change in atheroma volume on IVUS between baseline and 18-month follow-up
Absolute change in atheroma volume; change in the percent obstructive volume
Following an eight-week washout phase, patients were randomized to aggressive lipid-lowering strategy using atorvastatin (80 mg) (n=253) or a moderate lipid-lowering strategy using pravastatin (40 mg) (n=249). Patients underwent IVUS at baseline. Treatment was to continue for 18 months, at which time a follow-up IVUS study was performed. C-reactive protein (CRP) was also measured at baseline and follow-up.
Baseline LDL levels did not differ by treatment arm (150.2 mg/dl in both arms, p=0.99). Follow-up LDL levels were lower in the atorvastatin arm (79 mg/dl vs. 110 mg/dl, p<0.001), as were total cholesterol levels (151 mg/dl vs. 188 mg/dl, p<0.001), but HDL levels only trended higher with atorvastatin (43 mg/dl vs. 45 mg/dl, p=0.06).
Atheroma volume showed a significant progression in the pravastatin arm (2.7% compared with baseline, p=0.001), but no difference in the atorvastatin arm (-0.4 compared with baseline, p=0.98; comparing change in atorvastatin arm vs. pravastatin arm p=0.02). Similar results were observed for the secondary endpoint of change in percent obstruction volume (1.6% with pravastatin, p<0.001 vs. baseline; 0.2% with atorvastatin, p=0.18 vs. baseline; comparing change in atorvastatin arm vs. pravastatin arm p=0.0002). Similar results were observed for the change in percent obstructive volume in the subgroup analyses.
In a post-hoc analysis restricted to patients in the pravastatin arm whose LDL was <100 (67%, 167/249), the percent change in atheroma volume still showed progression (1.9%, p=0.01 compared with baseline). CRP decreased 36.4% in the atorvastatin arm versus 5.2% in the pravastatin arm (p<0.0001). There were no differences in adverse events, death (n=1 in each arm), or myocardial infarction (1.5% with atorvastatin and 2.1% with pravastatin).
Among patients with symptomatic CAD and elevated LDL, use of an aggressive lipid-lowering strategy through treatment with 80 mg atorvastatin was associated with a reduction in the primary endpoint of percent change in atheroma volume compared with a more moderate lipid-lowering strategy through treatment with 40 mg pravastatin.
While the data were provocative, the primary endpoint used an IVUS endpoint and the trial was not designed to assess mortality or clinical events. A much larger trial would be needed to assess superiority of one statin over another for these endpoints. American Heart Association/American College of Cardiology guidelines currently recommend statin therapy (as a class) for reduction of LDL levels to <100 mg/dl.
Nissen SE, et al. Effect of Intensive Compared With Moderate Lipid-Lowering Therapy on Progression of Coronary Atherosclerosis: A Randomized Controlled Trial. JAMA 2004;291 1071-1080.
Presented by Dr. Steven E. Nissen at the November 2003 American Heart Association Annual Scientific Sessions, Orlando, FL.
Keywords: Pyrroles, Cholesterol, Coronary Artery Disease, Myocardial Infarction, C-Reactive Protein, Follow-Up Studies, Plaque, Atherosclerotic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pravastatin, Heptanoic Acids, Hypercholesterolemia
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