ArticlesLong-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up
Introduction
Trials have shown that inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase reduce the risk of death and major cardiovascular events after acute myocardial infarction1, 2, 3 and unstable angina pectoris.3 The three large-scale trials—the Scandinavian Simvastatin Survival Study (4S), the Cholesterol and Recurrent Events (CARE) study, and the Long-term Intervention with Pravastatin in Ischaemic Disease study (LIPID)—suggested a possible lag in the treatment effect of 1–2 years after treatment begins. The LIPID trial was terminated early, in 1997, owing to clear evidence of survival benefits with pravastatin treatment. At this time, there were few data on the long-term effectiveness or safety of HMG-CoA reductase inhibitors beyond 5–6 years of treatment. Therefore, after the termination of the LIPID study, all patients were offered pravastatin therapy, with the plan to assess outcomes and safety over at least a further 2 years. We also planned to assess the effects of pravastatin therapy in important subgroups of patients for which the initial study was not powerful enough to show independent significant effects. These subgroups included women, patients aged 70 years or older, and those with total plasma cholesterol concentrations of less than 5·5 mmol/L.
Section snippets
Double-blind period
The design and results of the original study have been published.3, 4 This randomised placebo-controlled trial was undertaken at 87 centres in Australia and New Zealand, and involved 9014 patients who had had an acute myocardial infarction or a hospital discharge diagnosis of unstable angina pectoris 3–36 months before study entry and whose total cholesterol concentration was 4·0–7·0 mmol/L. Patients were randomly assigned pravastatin 40 mg per day or placebo in addition to their usual
Results
Between June, 1990, and December, 1992, 9014 patients were randomised into the LIPID study (figure 1). Patients were followed up during the double-blind phase of the trial for a mean of 6·0 years; one patient was lost to follow-up. Of the 7882 patients alive at the end of this phase, 7680 (97%) consented to long-term follow-up; 3914 had been initially assigned pravastatin (pravastatin group) and 3766 placebo (placebo group). The randomised groups were well balanced for baseline characteristics,
Discussion
The main LIPID study showed that pravastatin reduced total mortality and all prespecified cardiovascular outcomes in patients with previous acute coronary syndromes and average baseline cholesterol concentrations. These effects were seen across a broad range of subgroups and lipid concentrations and were in addition to contemporary medical treatments as used at the time.3 With extended follow-up, the LIPID study has now shown that the benefits of the first 6 years of cholesterol-lowering
References (28)
- et al.
Long-term risk stratification for survivors of acute coronary syndromes: results from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study
J Am Coll Car dial
(2001) - et al.
Fifteen-year mortality in coronary drug project patients: long-term benefit with niacin
J Am Coll Cardiol
(1986) - et al.
Follow-up study of patients randomised in the Scandinavian Simvastatin Survival Study (4S) of cholesterol lowering
Am J Car diol
(2000) - et al.
Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins
Atherosclerosis
(2000) - et al.
Do statins cause cancer? A meta-analysis of large randomised clinical trials
Am J Med
(2001) - et al.
Hypercholesterolaemia as a risk factor for coronary heart disease in the Asia-Pacific region: the ASPAC study
Atherosclerosis
(2000) - et al.
Mortality by cause for eight regions of the world: Global Burden of Disease Study
Lancet
(1997) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Lancet
(1994)- et al.
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels
N Engl J Med
(1996) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels
N Engl J Med
(1998)
Design features and baseline characteristics of the LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease) study: a randomised trial in patients with previous acute myocardial infarction and/or unstable angina pectoris
Am J Cardiol
Effects of pravastatin on mortality in patients with and without coronary heart disease across a broad range of cholesterol levels: the Prospective Pravastatin Pooling project
Eur Heart J
Cost of prevention. The case of lipid lowering
Circulation
Cited by (244)
Prevention of preeclampsia
2024, Best Practice and Research: Clinical Obstetrics and GynaecologyDegree of Risk Factor Control and Incident Cardiovascular Diseases in Patients With Hypertension
2024, Mayo Clinic ProceedingsCirculating biomarkers in familial cerebral cavernous malformation
2024, eBioMedicineDegree of Joint Risk Factor Control and Incident Heart Failure in Hypertensive Patients
2023, JACC: Heart FailureManagement of depression in patients with coronary artery disease: A systematic review
2023, Asian Journal of PsychiatryTime Course of LDL Cholesterol Exposure and Cardiovascular Disease Event Risk
2020, Journal of the American College of Cardiology
Members listed at end of paper