The Lipoprotein and Coronary Atherosclerosis Study (LCAS): Lipid and Metabolic Factors Related to Atheroma and Clinical Events - LCAS


The lipoprotein and coronary atherosclerosis study (LCAS) was a single-center, randomized, double-blind, placebo-controlled study to evaluate the effect of fluvastatin on reducing progression of coronary lesions as measured by quantitative coronary angiography (QCA) among patients with mildly elevated low-density lipoprotein (LDL) cholesterol.


Fluvastatin will reduce progression of coronary lesions in patients with mildly elevated LDL cholesterol.

Study Design

Study Design:

Patients Enrolled: 429
Mean Follow Up: 2.5 years
Mean Patient Age: 35-75
Female: 19

Patient Populations:

Men and women aged 35-75 years with a mean LDL cholesterol concentration from three separate determinations of 115-190 mg/dl on a prescribed National Cholesterol Education Program diet. Also, angiographic evidence ≥1 coronary lesion causing 30-75% diameter stenosis by caliper measurements in a coronary artery untreated by angioplasty and not 100% occluded. At least two of the three main coronary arteries had to be visualized by angiography, untreated by angioplasty, and <100% occluded. Mean fasting triglyceride levels had to be <300 mg/dl in all patients and <250 mg/dl in patients assigned to cholestyramine.


More than 50% stenosis of the left main coronary artery, prior CABG, uncontrolled hypertension, diabetes mellitus requiring treatment with insulin or an oral hyperglycemic agent, and fasting blood glucose >170 mg/dl

Primary Endpoints:

Within-patient per-lesion change in minimum luminal diameter of qualifying lesions assessed using QCA

Secondary Endpoints:

Time to first clinical event (non-CAD death, CAD death, nonfatal MI, unstable angina, CABG, or PTCA)

Drug/Procedures Used:

Patients were randomized into two treatment arms: fluvastatin (20 mg daily) or placebo. The arms were then subdivided into those with baseline LDL >160 mg/dl, who were additionally given cholestyramine up to 12 g/day, and those with LDL <160 mg/dl, who were given only the study medication. The groups were followed for 2.5 years.

Concomitant Medications:

A total of 106 patients (57 in the fluvastatin arm; 51 in the placebo arm) were assigned to adjunctive cholestyramine, up to 12 g/day, for baseline LDL greater 160 mg/dl.

Principal Findings:

A total of 429 patients (349 men and 80 women) were randomized. The mean age for all groups ranged from 57 to 59 years. The groups were well matched at baseline in terms of percent female, blood pressure, body mass index, smoking status, mean plasma glucose, and history of coronary artery disease (CAD). Baseline mean total cholesterol for all groups ranged from 211 to 252 mg/dl, mean LDL ranged from 137 to 173 mg/dl, and mean HDL ranged from 43 to 46 mg/dl.

For the primary endpoint, treatment with fluvastatin yielded significant coronary lesion benefit compared to placebo. Average change in minimum luminal diameter was -0.100 mm for all placebo patients and -0.028 mm for all fluvastatin patients (p<0.01). For placebo alone, the change was -0.094 mm and for fluvastatin alone -0.024 mm (p<0.02). For the secondary endpoint, fewer patients receiving fluvastatin had clinical events (non-CAD death, CAD death, nonfatal myocardial infarction [MI], unstable angina, coronary artery bypass grafting [CABG], or percutaneous transluminal coronary angioplasty [PTCA]).

The event rates for the four groups were 31 for placebo alone, 41 for all placebo patients, 20 for fluvastatin alone, and 31 for all fluvastatin. Differences in occurrence of clinical events were seen after 12 weeks of treatment, suggesting that fluvastatin may improve arterial and arteriolar function early during therapy.


Among patients with mildly elevated LDL cholesterol, treatment with fluvastatin was associated with a reduction in the progression of coronary arterial lesions and a reduction in the incidence of clinical events compared with placebo.


Herd JA. The lipoprotein and coronary atherosclerosis study (LCAS): lipid and metabolic factors related to atheroma and clinical events. Am J Med 1998;104:42S-49S.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Smoking

Keywords: Coronary Artery Disease, Myocardial Infarction, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Fatty Acids, Monounsaturated, Constriction, Pathologic, Hypercholesterolemia, Angioplasty, Balloon, Coronary, Smoking, Cholestyramine Resin, Lipoproteins, LDL, Coronary Angiography, Indoles, Triglycerides, Coronary Artery Bypass

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