Long-Term Intervention With Pravastatin in Ischemic Disease - LIPID
The goal of the trial was to compare the effects of pravastatin versus placebo in patients with coronary heart disease (CHD) for the prevention of cardiac death.
Contribution to the Literature: The LIPID trial showed that in patients with CHD, pravastatin reduced the risk of CHD death.
Patients Enrolled: 9,014; 10-year follow-up: 7,721
Mean Follow-up: 6.1 years + 10-year follow-up
Mean Patient Age: 31-75 years
Acute myocardial infarction (MI) or had a hospital discharge diagnosis of unstable angina between 3 and 36 months before study entry. Patients entered an 8-week-long single-blind placebo run-in phase during which they received dietary advice aimed at reducing their fat intake to <30% of total energy intake. For patients to qualify for the study, the plasma total cholesterol level measured 4 weeks before randomization was required to be 155-271 mg/dl, and the fasting triglyceride level <445 mg/dl (5.0 mmol/L).
Clinically significant medical or surgical event within 3 months before study entry, cardiac failure, renal or hepatic disease, or current use of any cholesterol-lowering agents
The primary study outcome was death from CHD. Deaths from CHD were further classified as death due to fatal MI, sudden death, death in the hospital after possible MI, or death due to heart failure or another coronary cause.
Secondary outcomes were death from any cause; death from cardiovascular causes; death from CHD or nonfatal MI; MI; stroke; nonhemorrhagic stroke; coronary revascularization (coronary angioplasty, coronary artery bypass surgery, or both); number of days in the hospital; serum lipid levels; and the relation of changes in lipid levels to the occurrence of cardiovascular endpoints.
In a double-blind, randomized trial, the effects of pravastatin (40 mg daily) with those of a placebo over a mean follow-up period of 6.1 years in 9,014 patients who were 31-75 years of age were compared. The patients had a history of MI or hospitalization for unstable angina and initial plasma total cholesterol levels of 155-271 mg/dl. Both groups received advice on following a cholesterol-lowering diet. The primary study outcome was mortality from CHD.
Death from CHD occurred in 8.3% of the patients in the placebo group and 6.4% of those in the pravastatin group, a relative reduction in risk (RRR) of 24% (95% confidence interval [CI] 12-35%; p < 0.001). Overall mortality was 14.1% in the placebo group and 11.0% in the pravastatin group (RRR 22%; 95% CI 13-31%; p < 0.001).
The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin; these outcomes included MI (RR 29%; p < 0.001), death from CHD or nonfatal MI (24% RR; p < 0.001), stroke (RR 19%; p = 0.048), and coronary revascularization (RR 20%; p < 0.001).
The effects of treatment were similar for all predefined subgroups. There were no clinically significant adverse effects of treatment with pravastatin.
Cumulative events at 16 years:
- CHD death: 19.9% vs. 21.7% (p = 0.009), respectively, for pravastatin vs. placebo
- All-cause death: 40.8% vs. 43.4% (p = 0.003), respectively, for pravastatin vs. placebo
- Cancer death: 10.7% vs. 10.3% (p = 0.87), respectively, for pravastatin vs. placebo
Pravastatin therapy was associated with a reduction in mortality from CHD and overall mortality, as compared with the rates in the placebo group, as well as the incidence of all prespecified cardiovascular events in patients with a history of MI or unstable angina who had a broad range of initial cholesterol levels. Results appeared to be maintained for the next 10 years.
Hague WE, Simes J, Kirby A, et al., on behalf of the LIPID Study Investigators. Long-term effectiveness and safety of pravastatin in patients with coronary heart disease: sixteen years of follow-up of the LIPID study. Circulation 2016;133:1851-60.
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57.
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