Rationale and design of the Department of Veterans Affairs high-density lipoprotein cholesterol Intervention Trial (HIT) for secondary prevention of coronary artery disease in men with low high-density lipoprotein cholesterol and desirable low-density lipoprotein cholesterol

https://doi.org/10.1016/0002-9149(93)90708-KGet rights and content

Abstract

Although a large body of epidemiologic evidence suggests that low levels of high-density lipoprotein (HDL) cholesterol are strongly associated with an increased risk of coronary artery disease (CAD), no large-scale clinical trials focusing on this association have been reported. This report describes the rationale and design of the Department of Veterans Affairs HDL Intervention Trial (HIT), a multicenter, randomized, controlled clinical trial designed to determine whether lipid therapy reduces the combined incidence of CAD death and nonfatal myocardial infarction in men with established CAD who have low levels of HDL cholesterol with “desirable” levels of low-density lipoprotein (LDL) cholesterol. Twenty-five hundred men with CAD and HDL cholesterol ≤40 mg/dl, LDL cholesterol ≤140 mg/dl, and triglycerides ≤300 mg/dl are being recruited at 20 Department of Veterans Affairs medical centers, randomized to either gemfibrozil or placebo, and followed in a double-blind manner for an average of 6 years. In this population, gemfibrozil is expected to increase HDL cholesterol by 10 to 15%, have a negligible effect on LDL cholesterol, and lower triglycerides by 30 to 40%. Because an estimated 20 to 30% of patients with CAD have a low HDL cholesterol as their primary lipid abnormality, the results of this trial are expected to have far-reaching clinical implications.

References (56)

  • E Lakatos

    Sample size determination in clinical trials with time-dependent rates of losses and noncompliance

    Controlled Clin Trials

    (1986)
  • SM Grundy et al.

    The place of HDL in cholesterol management: A perspective from the National Cholesterol Education Program

    Arch Intern Med

    (1989)
  • JD Rutherford et al.

    Chronic ischemic heart disease

  • MR Criqui

    Cholesterol, primary and secondary prevention, and all-cause mortality

    Ann Intern Med

    (1991)
  • J Pekkanen et al.

    Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease

    N Engl J Med

    (1990)
  • J Franzen et al.

    Reduced high density lipoproteins as a risk factor after acute myocardial infarction

    Acta Med Scand

    (1987)
  • Rubins HB, Schectman G, Wilt TJ, Iwane MK. High prevalence of isolated low HDL-cholesterol in community-living men with...
  • The Expert Panel

    Report of the National Cholesterol Education Program Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults

    Arch Intern Med

    (1988)
  • DJ Gordon et al.

    High-density lipoprotein — the clinical implications of recent studies

    N Engl J Med

    (1989)
  • G Assman et al.

    Prospective Cardiovascular Meunster Trial

    (1986)
  • WB Kannel et al.

    Cholesterol in the prediction of atherosclerotic disease: new perspectives based on the Framingham Study

    Ann Intern Med

    (1979)
  • MJ Stampfer et al.

    A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction

    N Engl J Med

    (1991)
  • V Manninen et al.

    Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study

    JAMA

    (1988)
  • DJ Gordon et al.

    High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: The Lipid Research Clinics Coronary Primary Prevention Trial

    Circulation

    (1986)
  • DH Blankenhorn et al.

    Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts

    JAMA

    (1987)
  • G Brown et al.

    Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B

    N Engl J Med

    (1990)
  • MH Frick et al.

    Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia

    N Engl J Med

    (1987)
  • Cited by (90)

    • The complexity of HDL

      2010, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
      Citation Excerpt :

      Following the initial demonstration of the correlation between low levels of plasma alpha lipoproteins and increased risk for CAD [1], large population studies including the Framingham Heart Study [2], the Lipid Research Clinics Prevalence Study [3], the Trømso Heart Study [4], the Prospective Cardiovascular Münster Trial [5], the Physician's Health Study [6], and others [7] confirmed this relationship, with several of these studies indicating a low level of HDL-C to be the single strongest predictor of CAD events [8]. This relationship is independent of other major coronary risk factors, as well as plasma triglyceride levels [9], and is present in both men and women, the elderly, and those with and without CAD at baseline [8]. Confounding this general population trend, however, are genetic HDL deficiency states that are frequently but not always associated with increased risk for atherosclerosis.

    • Efficacy of gemfibrozil in the primary prevention of atrial fibrillation in a large randomized controlled trial

      2009, American Heart Journal
      Citation Excerpt :

      The VA-HIT was a multicenter, double-blinded, randomized controlled trial that tested whether gemfibrozil was effective in secondary prevention of CHD in men with low levels of high-density lipoprotein. Trial design and results have previously been published elsewhere.12,14 Briefly, men <74 years old with a history of CHD, high-density lipoprotein cholesterol ≤40 mg/dL (≤3.6 mmol/L), low-density lipoprotein cholesterol ≤140 mg/dL, and triglyceride level ≤300 mg/dL were randomized to gemfibrozil 1,200 mg/d or matching placebo.

    • Lipid Management in the Geriatric Patient

      2009, Endocrinology and Metabolism Clinics of North America
    • Statin, the black box

      2008, Archives of Cardiovascular Diseases
    View all citing articles on Scopus

    See Appendix.

    View full text