Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: The LIPID trial follow-up

John Simes, R. J. Simes, D. Hunt, A. Kirby, A. Tonkin, A. Keech, P. Aylward, D. Colquhoun, P. Glasziou, W. Hague, S. MacMahon, P. Thompson, M. West, H. White

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    Abstract

    Background: The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study showed that pravastatin therapy over 6 years reduced mortality and cardiovascular events in patients with previous acute coronary syndromes and average cholesterol concentrations. We assessed the longer-term effects of initial treatment with pravastatin on further cardiovascular events and mortality over a total follow-up period of 8 years. Methods: In the main trial, 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol concentration of 4.0-7.0 mmol/L were randomly assigned pravastatin 40 mg daily or placebo and followed up for 6 years. Subsequently, all patients were offered open-label pravastatin for 2 more years. Major cardiovascular events and adverse events were compared according to initial treatment assignment. Findings: 7680 (97% of those still alive) had 2 years of extended follow-up. 3766 (86%) of those assigned placebo and 3914 (88%) assigned pravastatin agreed to take open-label pravastatin. During this period, patients originally assigned pravastatin had almost identical cholesterol concentrations to those assigned placebo, but a lower risk of death from all causes (219 [5.6%] vs 255 [6.8%], p=0.029), coronary heart disease (CHD) death (108 [2.8%] vs 137 [3.6%], p=0.026), and CHD death or non-fatal myocardial infarction (176 [4.5%] vs 196 [5.2%], p=0.08). Over the total 8-year period, all-cause mortality was 888 (19.7%) in the group originally assigned placebo and 717 (15.9%) in the group originally assigned pravastatin, CHD mortality was 510 (11.3%) versus 395 (8.8%), myocardial infarction was 570 (12.7%) versus 435 (9.6%; each p<0.0001), and stroke was 272 (6.0%) versus 224 (5.0%; p=0.015). Stronger evidence of separate treatment benefits than in the main trial was seen in important prespecified subgroups (women, patients aged ≥70 years, and those with total cholesterol <5.5 mmol/L). Pravastatin had no significant adverse effects. Interpretation: The evidence of sustained treatment benefits and safety of long-term pravastatin treatment reinforces the importance of long-term cholesterol-lowering treatment for almost all patients with previous CHD events.

    Original languageEnglish
    Pages (from-to)1379-1387
    Number of pages9
    JournalLancet
    Volume359
    Issue number9315
    DOIs
    Publication statusPublished - 20 Apr 2002

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    Simes, J., Simes, R. J., Hunt, D., Kirby, A., Tonkin, A., Keech, A., Aylward, P., Colquhoun, D., Glasziou, P., Hague, W., MacMahon, S., Thompson, P., West, M., & White, H. (2002). Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: The LIPID trial follow-up. Lancet, 359(9315), 1379-1387. https://doi.org/10.1016/S0140-6736(02)08351-4