efficacy and safety study of ezetimibe (sch 58235, mk-0653) in addition to atorvastatin in participants with coronary heart disease or multiple cardiovascular risk factors (p00693/mk-0653-030)

Conditions: Hypercholesterolemia

Summary: the overall objective is to evaluate the efficacy and safety of ezetimibe (sch 058235/mk-0653) 10 mg administered daily in conjunction with atorvastatin in participants with heterozygous familial hypercholesterolemia (hefh) or in participants with coronary heart disease (chd) or multiple cardiovascular risk factors (≥2 risk factors) and primary hypercholesterolemia not controlled by a starting dose (10 mg/day) of atorvastatin. the primary hypothesis is that the coadministration of ezetimibe 10 mg/day with atorvastatin therapy will result in a significantly greater proportion of participants achieving target low-density lipoprotein cholesterol (ldl-c) (≤100 mg/dl) when compared to the atorvastatin administered alone.


Eligibility criteria:
inclusion criteria: * primary hypercholesterolemic participants with known coronary heart disease (chd) or multiple risk factors for chd (≥2) not meeting the target low-density-lipoprotein cholesterol (ldl-c) of ≤100 mg/dl (2.59 mmol/l), with plasma ldl-c ≥130 mg/dl (3.37 mmol/l) and plasma triglycerides (tg) ≤350 mg/dl (3.99 mmol/l) while on starting-dose (10 mg) atorvastatin at least 4 weeks before initial qualifying lipid determination. * participants with heterozygous familial hypercholesterolemia (hefh) not meeting the target ldl-c of ≤100 mg/dl (2.59 mmol/l), with plasma ldl-c ≥130 mg/dl (3.37 mmol/l) and plasma tg ≤350 mg/dl (3.99 mmol/l) while on starting-dose (10 mg) atorvastatin for at least 4 weeks before initial lipid qualifying determination. hefh is defined by: a) genetic testing; or b) ldl-c \>190 mg/dl (4.9 mmol/l) and at least one of the following: (1) xanthomata in first or second degree relative; (2) family history of myocardial infarction under age 60 years in a first degree relative or family history of myocardial infarction under age 50 years in a second degree relative; (3) family history of total cholesterol (tc) \>290 mg/dl (\>7.5 mmol/l) in a first or second degree relative. * all women must have a negative pregnancy test prior to study entry. women of child-bearing potential must agree to practice an effective barrier method of birth control for the duration of the study, as well as for 1 month following study completion. * postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen replacement therapy (ert), estrogen/progestin hormone replacement therapy (hrt) or raloxifene regimen during the study period. * participants must be willing to observe the national cholesterol education program (ncep) step i diet as determined by a ratio of ingested saturated fat and cholesterol to calories (riscc) score not greater than 24 throughout this study. ability to complete diet diaries needs to be demonstrated. exclusion criteria: * individuals with a history of mental instability, drug/alcohol abuse within the past 5 years or individuals who have been treated or are being treated for severe psychiatric illness which in the opinion of the investigator, may interfere with optimal participation in the study. * underlying disease likely to limit life span to less than 1 year. * participants who have previously been randomized in any of the studies evaluating ezetimibe. * participants with known hypersensitivity or any contraindication to atorvastatin * pregnant or lactating women. * participants with congestive heart failure new york heart association (nyha) class iii or iv. * participants with uncontrolled cardiac arrhythmias * participants with myocardial infarction, coronary bypass surgery or angioplasty within 3 months of study entry. * participants with unstable or severe peripheral artery disease within 3 months of study entry. * participants with unstable angina pectoris. * participants with disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation. * participants with uncontrolled (as determined by hemoglobin a1c \[hba1c\]) or newly diagnosed (within 1 month of study entry) diabetes mellitus. * participants with uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins. clinically euthyroid participants on replacement doses of thyroid hormone are eligible for enrollment. * participants with known impairment of renal function (creatinine \>2.0 mg/dl), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram). * participants with active or chronic hepatobiliary or hepatic disease (participants with aspartate aminotransferase (ast) or alanine aminotransferase (alt) \>2 times the upper limit of the central laboratory reference range \[uln\] will be excluded). * participants who are known to be human immunodeficiency virus (hiv) positive. * participants with known coagulopathy (prothrombin time \[pt\] or partial thromboplastin time \[ptt\] at visit 2 \>1.25 times control).