Cholesterol Lowering Atherosclerosis Study (I and II) - CLAS I AND II

Description:

Colestipol plus niacin for atherosclerosis progression after CABG surgery.

Hypothesis:

Lowering blood cholesterol has directly beneficial effects on human atherosclerotic lesions.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 265
Mean Follow Up: 2 years for CLAS I; 4 years for CLAS II
Mean Patient Age: 54.2
Female: 0

Patient Populations:

Nonsmoking men, 40 to 59 years of age
Progressive atherosclerosis, confirmed through angiographic review
CABG not involving valve replacement at least 3 months before start of study
Fasting blood cholesterol levels at entry in the range of 185-350 mg/dl

Exclusions:

Bilateral femoral artery surgery
Diabetes mellitus
Hypertension (diastolic blood pressure > 115 mm Hg)
Thyroid disease
Renal insufficiency
Fasting blood triglyceride levels > 500 mg/dl
Congestive heart failure
Major arrhythmia
QRS width exceeding 0.12 s
Weight exceeding 1.5 times ideal weight as determined by MRFIT criteria

Primary Endpoints:

Global coronary change score

Secondary Endpoints:

Per-lesion treatment effects in native coronary arteries and bypass grafts

Drug/Procedures Used:

Both groups: lipid-lowering diet intervention, more stringent in test drug group than placebo group to enhance the differential in blood cholesterol response between the groups.
Study drug group: Colestipol hydrochloride, 15g bid, and niacin, 3-12 g/day (as 3 divided doses).

Concomitant Medications:

Aspirin, 325 mg before breakfast for the first 14 days. No lipid-lowering agents except study medications were allowed, nor were anticoagulants or platelet-active drugs.

Principal Findings:

CLAS I:
After 2 years, there was a 26% reduction in total plasma cholesterol, a 43% reduction in low-density lipoprotein cholesterol, plus a simultaneous 37% elevation of high-density lipoprotein cholesterol.

This resulted in a significant reduction in the average number of lesions per subject that progressed (p < 0.03) and in the percentage of subjects with new atheroma formation (p <<0.03) in native coronary arteries.

The percentage of subjects with new lesions (p < 0.04) or any adverse changes in bypass grafts (p< 0.03) was significantly reduced.

Deterioration in overall coronary status was significantly less in drug-treated subjects than placebo-treated subjects (p < 0.001).

Atherosclerosis regression, as indicated by perceptible improvement in overall coronary status, occurred in 16.2% of drug-treated vs 2.4% of placebo treated patients (p=0.002)

CLAS II subgroup
Changes in blood lipid, lipoprotein-cholesterol, and apolipoprotein levels were maintained.

Significantly more drug-treated subjects than placebo-treated subjects demonstrated nonprogression (52% vs 15%) and regression (18% vs 6%) in native coronary lesions.

Significantly fewer drug-treated subjects than placebo-treated subjects developed new lesions in native coronary arteries (14% vs 40%) and bypass grafts (16% vs 38%).

Interpretation:

Combined therapy with colestipol plus niacin can provide significant benefits in nonsmoking men. However, we caution that the aggressive regimen used in this study requires close supervision because of recognized side effects caused by the use of colestipol plus niacin. The CLAS II study reaffirms the benefits of early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects.

References:

1. JAMA 1987;257:3233-40. Final results
2. JAMA 1990;264:3013-17. 4-year follow-up

Clinical Topics: Cardiac Surgery, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Interventions and Coronary Artery Disease, Diet

Keywords: Cholesterol, Coronary Artery Disease, Atherosclerosis, Plaque, Atherosclerotic, Colestipol, Niacin, Coronary Artery Bypass, Fasting


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