the effects of ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in high cholesterol and coronary heart disease study (p04039am2)(completed)

Conditions: Hypercholesterolemia; Coronary Disease

Summary: this study is being conducted to compare the efficacy, safety, and tolerability of ezetimibe/simvastatin 10/20 mg when administered daily versus doubling the dose of simvastatin to 40 mg in patients with hypercholesterolemia and coronary heart disease.


Eligibility criteria:
inclusion criteria: * subjects must have documented coronary heart disease (chd). for the purposes of this study, chd will include one or more of the following features: documented stable angina (with evidence of ischemia on exercise testing); history of myocardial infarction; history of percutaneous coronary intervention \[pci\] (primarily pci with or without stent placement); symptomatic peripheral vascular disease (claudication); documented history of atherothrombotic cerebrovascular disease; and/or documented history of unstable angina or non-q wave myocardial infarction. * subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent. * history of myocardial infarction (heart attack). * subjects must be \>= 18 years and \<= 75 years of age. * subjects must have an ldl-c concentration \>= 2.6 mmol/l (100 mg/dl) to \<= 4.1 mmol/l (160 mg/dl) at the time of randomization (visit 3/baseline visit). * subjects must have triglyceride concentrations of \< 3.99 mmol/l (350 mg/dl) at (visit 3 baseline visit). * subject must be currently taking simvastatin 20 mg daily. * subjects must have liver transaminases (alt \[alanine aminotransferase\], ast \[aspartate aminotransferase\]) \< 50% above the upper limit of normal, with no active liver disease, and ck (creatine kinase) \< 50% above the upper limit of normal at visit 3 (baseline visit). * clinical laboratory tests (complete blood count \[cbc\], blood chemistries, urinalysis) must be within normal limits or clinically acceptable to the investigator at visit 3 (baseline visit). * subjects must have maintained a cholesterol-lowering diet and exercise program for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study. * subjects must report a stable weight history for at least 4 weeks prior to entry into study at visit 3 (baseline visit). * women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study. * women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed intrauterine device \[iud\], condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation). * subjects must be free of any clinically significant diseases other than hyperlipidemia or coronary heart disease that would interfere with study evaluations. * subjects must understand and be able to adhere to the dosing and visit schedules, and must agree to remain on their cholesterol-lowering diet and their exercise regimen for the duration of the study. exclusion criteria: * subjects whose body mass index (bmi = weight \[kg\]/height2 \[m\]) is \>= 35 kg/m\^2 at visit 3 (baseline visit). * subjects who consume \> 14 alcoholic drinks per week. (a drink is: a can of beer, glass of wine, or single measure of spirits). * any condition or situation which, in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study. * women who are pregnant or nursing. exclusion criteria: subjects who have the following medical conditions: * congestive heart failure defined by new york heart association (nyha) as class iii or iv. * uncontrolled cardiac arrhythmia. * myocardial infarction, acute coronary insufficiency, coronary artery bypass surgery, or angioplasty within 3 months of visit 3 (baseline visit). * unstable or severe peripheral artery disease within 3 months of visit 3 (baseline visit). * newly diagnosed or currently unstable angina pectoris (chest pain). * uncontrolled hypertension (treated or untreated) with systolic blood pressure \> 160 mm hg or diastolic \> 100 mm hg at visit 3 (baseline visit). * type i or type ii diabetes mellitus. * uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, i.e., secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism (thyroid stimulating hormone \[tsh\] above upper limit of normal) at visit 3. subjects with a history of hypothyroidism who are on a stable therapy of thyroid hormone replacement for at least 6 weeks are eligible for enrollment if tsh levels are within normal limits at visit 3 (baseline visit). * impaired renal function (creatinine \> 2.0 mg/dl) or nephrotic syndrome at visit 3 (baseline visit). * disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation. * known human immunodeficiency virus (hiv) positive. * cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas). * history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy. exclusion criteria: subjects who are on any of the following concomitant medications: * subjects who have not observed the designated wash-out period for any of the prohibited medications. * subjects who have not stopped taking various prohibited medications for a minimum period of time before visit 3, including amiodarone hydrochloride (6 months) and probucol (12 months). * subjects currently consuming large amounts of grapefruit juice (\> 1 liter/day). * oral corticosteroids, unless used as replacement therapy for pituitary/adrenal disease and the subject is on a stable regimen for at least 6 weeks prior to visit 3 (baseline visit). * subjects who are currently using cardiovascular medication (e.g. antihypertensive, antiarrhythmic) and have not been on a stable regimen for at least 6 weeks prior to visit 3 (baseline visit) and it is expected to change during the study. * subjects who are currently using psyllium, other fiber-based laxatives, and/or any other over-the-counter (otc) therapy known to affect serum lipid levels (phytosterol margarine), and have not been on a stable regimen for at least 5 weeks prior to study entry visit 3 (baseline visit) and who do not agree to remain on this regimen throughout the study. * subject who are currently using orlistat or sibutramine. * subjects who are currently using amiodarone hydrochloride. * subjects who are currently using danazol. * subjects who are currently using coumarin anticoagulants (warfarin). * subjects who are using (at the screening visit / visit 1) any statin other than simvastatin 20 mg, or ezetimibe alone or in combination with any statin (including the fixed combination with simvastatin).