Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries II - PLAC-II

Oct 04, 2004
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Date Published:
01/01/1995
Date Updated:
10/04/2004
Original Posted Date:
10/04/2004
References

Description:

B-mode ultrasonography to monitor atherosclerotic disease progression.

Hypothesis:

IMT might be used as an approximate surrogate for coronary disease.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 151
Mean Follow Up: 36 months

Patient Populations:

Presence of coronary artery disease (CAD) defined as a history of heart attack or cardiac catheterization demonstrating >50% stenosis of at least one coronary artery.
Diet-resistant LDL cholesterol between the 60th and 90th percentile for age and sex.
At least one qualifying extracranial lesion with an IMT of >1.3mm.

Exclusions:

Plasma triglyceride concentrations >350 mg/dL.
Uncontrolled heart failure.
Hypertension.
Hypo- or hyperthyroidism or other endocrine diseases.
Secondary hyperlipidemia.
Recent myocardial infarction (<6 months).
Severe or unstable angina pectoris.
Significant disease that might interfere with drug absorption.
Excessive ethanol consumption.
Treatment with certain drugs including corticosteroids, androgens, other lipid-lowering agents, or antacids containing aluminum salts.
Ultrasound examinations that were difficult to read or interpret or with significant carotid stenosis.

Primary Endpoints:

The rate of progression of the mean-maximum IMT.

Secondary Endpoints:

The combined endpoint of any coronary event and any death; effects on individual carotid artery segments (common, bifurcation, and internal carotid) and on clinical events.

Drug/Procedures Used:

B-mode ultrasound; pravastatin, 20 mg/day 3 to 4 hours after the evening meal, increased to 40 mg/day if LDL cholesterol did not fall below 110 mg/dL, or decreased to 10 mg/day if LDL cholesterol had fallen below 90 mg/dL.

Principal Findings:

Plasma concentrations of total cholesterol were lower with active treatment than with placebo (4.80 vs. 6.07 mmol/L [186 vs. 235 mg/dL], respectively) as were concentrations of low-density lipoprotein cholesterol (3.11 vs. 4.30 mmol/L [120 vs. 167 mg/dL], respectively).

Plasma concentrations of high-density lipoprotein2 cholesterol were higher with active treatment (0.16 vs. 0.14 mmol/L [6.1 vs. 5.5 mg/dL], respectively).

Active treatment resulted in a nonsignificant 12% reduction in progression of the mean-maximum IMT (from 0.068 to 0.059 mm/year) and a statistically significant 35% reduction in IMT progression in the common carotid.

Active treatment was also associated with a reduction in fatal and nonfatal coronary events [corrected] (p = 0.09) and of any fatal event plus nonfatal myocardial infarction (p = 0.04).

Interpretation:

Lowering LDL cholesterol is particularly beneficial in patients with prevalent coronary disease. The results are consistent with those of PLAC-I, an angiographic trial of LDL lowering with pravastatin, which showed a favorable effect of pravastatin on coronary atherosclerosis.

References:

1. Controlled Clinical Trials 1992;13:495-506. Study design
2. Am J Cardiol 1995;75:455-459 [published erratum appears in Am J Cardiol 1995;15;75(12):862]. Final results
3. American Journal of Cardiology 1995;76(9):54C-59C. Review

Keywords: Lipoproteins, LDL, Coronary Artery Disease, Myocardial Infarction, Secondary Prevention, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiac Catheterization, Pravastatin, Diet, Constriction, Pathologic


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