Context Statin drugs reduce both atherogenic lipoproteins and cardiovascular
morbidity and mortality. However, the optimal strategy and target level for
lipid reduction remain uncertain.
Objective To compare the effect of regimens designed to produce intensive lipid
lowering or moderate lipid lowering on coronary artery atheroma burden and
Design, Setting, and Patients Double-blind, randomized active control multicenter trial (Reversal
of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) performed at
34 community and tertiary care centers in the United States comparing the
effects of 2 different statins administered for 18 months. Intravascular ultrasound
was used to measure progression of atherosclerosis. Between June 1999 and
September 2001, 654 patients were randomized and received study drug; 502
had evaluable intravascular ultrasound examinations at baseline and after
18 months of treatment.
Interventions Patients were randomly assigned to receive a moderate lipid-lowering
regimen consisting of 40 mg of pravastatin or an intensive lipid-lowering
regimen consisting of 80 mg of atorvastatin.
Main Outcome Measures The primary efficacy parameter was the percentage change in atheroma
volume (follow-up minus baseline).
Results Baseline low-density lipoprotein cholesterol level (mean, 150.2 mg/dL
[3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL (2.85 mmol/L)
in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the atorvastatin
group (P<.001). C-reactive protein decreased 5.2%
with pravastatin and 36.4% with atorvastatin (P<.001).
The primary end point (percentage change in atheroma volume) showed a significantly
lower progression rate in the atorvastatin (intensive) group (P = .02). Similar differences between groups were observed for secondary
efficacy parameters, including change in total atheroma volume (P = .02), change in percentage atheroma volume (P<.001), and change in atheroma volume in the most severely diseased
10-mm vessel subsegment (P<.01). For the primary
end point, progression of coronary atherosclerosis occurred in the pravastatin
group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P = .001) compared with baseline. Progression did not occur in the
atorvastatin group (−0.4%; CI −2.4% to 1.5%; P = .98) compared with baseline.
Conclusions For patients with coronary heart disease, intensive lipid-lowering treatment
with atorvastatin reduced progression of coronary atherosclerosis compared
with pravastatin. Compared with baseline values, patients treated with atorvastatin
had no change in atheroma burden, whereas patients treated with pravastatin
showed progression of coronary atherosclerosis. These differences may be related
to the greater reduction in atherogenic lipoproteins and C- reactive protein
in patients treated with atorvastatin.