Asymptomatic Carotid Artery Plaque Study (ACAPS)
Asymptomatic Carotid Artery Plaque Study (ACAPS)
To determine whether warfarin or lovastatin alone or in combination retarded the progression
 of atherosclerotic plaques in the carotid arteries of high risk individuals with asymptomatic
 carotid stenosis. Also, to determine if a full scale trial was feasible.
BACKGROUND:

 At the present time, atherosclerosis of the major extracranial arteries to the brain is
 considered the cause of most strokes. Early intervention and stroke prevention utilized
 anti-coagulants such as coumadin and heparin. Results were largely equivocal due to the
 diverse nature of the underlying pathogenesis and due to problems that offset potential
 benefit. Emphasis gradually switched to aspirin and to other platelet anti-aggregant drugs
 because of mounting evidence that micro-emboli were a major element in transient ischemic
 attacks. Several studies have examined the potential benefit of aspirin in stroke prevention.
 The exact dose of aspirin that was maximally beneficial with minimal side effects was not
 completely established. There was evidence that low dose aspirin was as effective as higher
 doses. The American College of Chest Physicians (ACCP) made recommendations that if aspirin
 were issued as a primary anti-thrombotic agent, the dose should be 325 mg daily, except in
 patients with cerebrovascular disease in whom the lowest beneficial dose appeared to be one
 gram per day. The ACCP also pointed out that the risk of bleeding was substantially greater
 in patients with ischemic cerebrovascular disease and venous thromboembolism than in other
 high risk groups requiring anticoagulation. It advised that anticoagulant therapy was not
 needed, but that aspirin might be given at 325 mg per day.

 Lovastatin is a fungal metabolite that inhibits 3-hydroxy, 3-methyl glutaryl coenzyme A
 reductase, the rate-limiting enzyme of cholesterol biosynthesis in human cells including the
 liver. Inhibition of this pathway causes the cells to increase their low density lipoprotein
 receptor numbers to compensate, causing a reduction in circulating low density lipoprotein
 levels with a consequent drop in circulating plasma cholesterol levels. The drug also raises
 high density lipoprotein levels significantly. A favorable outcome of the trial will have
 major public health implications for the prevention and control of atherosclerosis and its
 complications.

 DESIGN NARRATIVE:

 Randomized, double-blind, factorial design. In this multicenter study, patients were assigned
 to one of four drug combination groups: active lovastatin/active warfarin, active
 lovastatin/warfarin placebo, lovastatin placebo/active warfarin, and lovastatin
 placebo/warfarin placebo. Daily aspirin was recommended for everyone. Ultrasound was
 performed for screening, at baseline and semiannually thereafter. Lipid profiles were
 obtained at screening, at baseline, monthly for the first three months, at six months, and
 annually thereafter, with beta quantification at baseline. Recruitment began in the tenth
 month of the trial and continued for one year, ending in September 1990. Treatment continued
 through the 51st month. Average treatment period was 2.7 years. Subjects were offered a
 dietary regimen for three months prior to receiving any drug therapy. Only those individuals
 whose lipid levels did not fall below a certain point continued in dietary intervention. The
 primary outcome measure was the three year change in mean maximum intimal-medial thickness
 (IMT) in twelve walls of the carotid arteries. Secondary outcomes included change in single
 maximum IMT and incidence of major cardiovascular events.

 In 1995, an R03 was awarded to Mark Espeland to extend analyses of the carotid B-mode
 ultrasound data through August, 1998.

 The study completion date listed in this record was obtained from the "End Date" entered in
 the Protocol Registration and Results System (PRS) record.
Men and women with early carotid atherosclerosis and moderately elevated LDL cholesterol
 between the 60th and 90th percentiles.