Effect of Intensive Compared With Moderate Lipid-Lowering Therapy on Progression of Coronary Atherosclerosis: A Randomized Controlled Trial.

Nissen, Steven E.; Tuzcu, E. Murat; Schoenhagen, Paul; Brown, B. Greg; Ganz, Peter; Vogel, Robert A.; Crowe, Tim; Howard, Gail; Cooper, Christopher J.; Brodie, Bruce; Grines, Cindy L.; DeMaria, Anthony N.

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 progression. 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 dis...

ATHEROSCLEROTIC plaque; STATINS (Cardiovascular agents); LIPOPROTEINS; ATHEROSCLEROSIS treatment; CORONARY arteries; HEALTH outcome assessment; CORONARY heart disease treatment; CHOLESTEROL; C-reactive protein; PREVENTION

JAMA: Journal of the American Medical Association, 2004, Vol 291, Issue 9, p1071

0098-7484

Academic Journal

10.1001/jama.291.9.1071