None listed
Conditions
Brief summary
This multicentre, double-blind, placebo-controlled clinical trial is designed to determine whether prolonged reduction in blood cholesterol with pravastatin, one of the class of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMG-CoA reductase) inhibitors, will reduce mortality from coronary heart disease in patients with a history of myocardial infarction or unstable angina pectoris. To qualify for entry, a patient must have a blood cholesterol level in the range 4.0 to 7.0 mmol/L, and must have suffered a myocardial infarction or have been admitted to hospital with unstable angina, within three months to three years prior to screening. The primary study outcome will be death due to coronary heart disease. Secondary analyses will be of death from all causes, combined incidence of non fatal myocardial infarction and fatal coronary heart disease, stroke (total and non-haemorrhagic), cardiovascular mortality, coronary revascularisation (CABG and coronary angioplasty), and number of days in hospital during the follow-up period. The goal of intervention is to reduce total blood cholesterol by an average of 25% in patients allocated pravastatin compared with those allocated placebo. To detect reliably the expected effect of such a cholesterol difference on the primary endpoint requires about 9,000 patients be randomised in equal numbers to pravastatin or placebo, and that follow-up of these patients continues for a minimum 5 years for each surviving patient.
Interventions
20mg pravastatin oral tablet twice daily for 6 years. Dosage will be halved if total cholesterol falls below 3.0 mmol/L on two successive follow-up visits.
Compliance will be assessed by site staff at follow up visits and subjects encouraged to take tablets as directed.
Sponsors
NHMRC Clinical Trials Centre, The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
31 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. ENTRY DIAGNOSIS: A. Patients who have suffered an acute myocardial infarction in the period three months to three years prior to screening, where acute myocardial infarction satisfies the following criteria: 1) Discharge diagnosis of acute myocardial infarction in hospital records, OR 2) Any 2 of the following 3: a. History of typical ischaemic pain lasting for at least 15 minutes and unresponsive to sublingual nitrates b. Elevation of CK enzymes to more than twice the upper limit of normal c. Development of new Q-Waves and/or evolutionary ST-T wave changes lasting at least one day. OR B. Patients who have been discharged from hospital with a diagnosis of unstable angina pectoris three months to three years prior to assessment, where unstable angina pectoris is defined as definite ischaemic pain increasing in frequency and duration, and/or angina occurring at rest. 2. SERUM CHOLESTEROL: Total cholesterol between 4.0 and 7.0 mmol/L, measured by the Central Lipid Laboratory in the 4 weeks prior to randomisation
Exclusion criteria
1. Patients who are unlikely to be available for the duration of follow-up: i) patients with life threatening illnesses other than coronary artery disease, who are not expected to survive for six years (such as organ transplants), or ii) those who are unreliable including those with known drug or alcohol related problems. 2. Any cardiac surgery, angioplasty, major surgery or major illness within the past three months. 3. Severely compromised cardiac function (whether due to ischaemic heart disease or not), manifest by either: i) New York Heart Association (NYHA) Class III or IV congestive heart failure (at the time of assessment). ii) Left ventricular ejection fraction less than 25% (if measured). 4. History of cerebrovascular disease, including completed stroke or transient ischaemic attack within three months. 5. Significant renal or hepatic disease (such as serum creatinine > 160 micromol/L, serum albumin <3.0 g/dl; bilirubin >30 micromol/L, serum ALT or AST >1.5x the upper limit of normal). 6. Any uncontrolled endocrine disease (particularly if likely to require hospitalisation); chronic pancreatitis; dysproteinaemia; porphyria; systemic lupus erythematosus. 7. Treatment with : (a) other lipid-lowering agents; (b) cyclosporin; (c) other investigational drugs. 8. Known hypersensitivity to HMG-CoA reductase inhibitors or serious adverse reactions from prior administration of HMG-CoA reductase inhibitors. 9. Significant gastrointestinal disease or surgery which might interfere with drug absorption. 10. Women of child-bearing potential (ie pre-menopausal, unless surgically sterilised) and lactating women. 11. Fasting triglyceride (as measured by the Central Lipid Laboratory) of greater than 5mmol/L
Outcome results
None listed