Effects of lipid lowering on coronary plaques and coronary events.

C linical trials evaluating the efficacy of interventions to lower serum total and LDL-cholesterol levels often use angiographic induction of regression and slowing of progression of coronary narrowing as endpoints.1,2 In the Program on the Surgical Control of the Hyperlipidemias (POSCH), Buchwald et al3 used partial ileal bypass and dietary management to lower total and LDL-cholesterol levels in men and women with healed myocardial infarction. At 5 years, there was a 35% reduction in combined CAD-related death and confirmed nonfatal myocardial infarction in the surgery group compared to the control group (dietary counseling alone; 125 vs 82, p 5 0.001). Mean serum total cholesterol levels were decreased by 23% (p ,0.0001) and LDL-cholesterol levels decreased by 38% (p ,0.0001). Follow-up of coronary arteriograms at 3, 5, 7, and 10 years demonstrated significantly less progression (p ,0.001) in the surgery group. The POSCH trial also reported a decrease in new coronary narrowing and some reversal of previously existing narrowing.3 Several angiographic trials have evaluated the ability of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and other lipid-lowering drugs to promote regression and slow progression of coronary atherosclerotic plaques in CAD patients. Overall, these trials have demonstrated a reduction in coronary events. Some major trials included the Multicentre Anti-Atheroma Study (MAAS), the Stanford Coronary Risk Intervention Project (SCRIP), and the Familial Atherosclerosis Treatment Study (FATS).4–6 In MAAS, patients treated with simvastatin 20 mg/day over 4 years had significantly less progression and more regression of their atherosclerotic disease combined when compared to placebo (p 5 0.02). Reductions in total and LDL-cholesterol levels were 23% and 31%, respectively, when compared to placebo. Although the study was not designed to look at clinical outcomes, fewer patients in the simvastatintreated group had coronary angioplasty or bypass procedures.4 In SCRIP, intensive risk reduction including diet, exercise, weight loss, smoking cessation, and lipid-lowering therapy was evaluated in patients with atherosclerosis. The study disclosed a reduced rate of progression of narrowing in coronary arteries (p ,0.02), fewer new narrowings per patient (p 5 0.06), and fewer segments with new narrowings (p 5 0.05).5 Mortality rates were similar, and hospitalization for cardiac causes were reduced. In the FATS trial, the efficacy of cholesterol-lowering drug therapy was evaluated in men with existing CAD.6 At 2.5 years, patients treated with lovastatin plus colestipol had a 33% reduction in serum total cholesterol, with reductions of 23% and 3% found in the colestipol plus niacin and placebo groups, respectively. Plaque regression, as measured by angiography, was more common in the treatment groups. The frequency of combined fatal and nonfatal myocardial infarction was lower in the drug treatment groups compared to placebo (lovastatin/colestipol 5 4%, niacin/colestipol 5 6%, placebo 5 19%). Clinical trial data indicate that the slowing of progression or regression of coronary atherosclerosis results in a decrease in coronary events. Although many of these trials were not designed to show the effect on clinical outcome, the results provide information consistent with cholesterol lowering trials such as the Scandinavian Simvastatin Survival Study (4S) and the Coronary and Recurrent Events (CARE) trials that evaluated clinical events as a primary outcome.7,8