Asymptomatic Carotid Artery Plaque Study (ACAPS)
Condition: Cardiovascular Diseases; Carotid Stenosis; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Heart Diseases; Vascular Diseases
MeSH terms: Carotid Stenosis; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Cardiovascular Diseases; Heart Diseases; Vascular Diseases; Arteriosclerosis
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): aspirin; lovastatin
Intervention type(s): Drug; Drug
Intervention MeSH terms: Aspirin; Lovastatin; L 647318; Dihydromevinolin
Allocation: Randomized
Masking: Double
Primary purpose: Prevention