Official Title: “CSP#363 - The VA HDL Intervention Trial (HIT): Secondary Prevention of Coronary Heart Disease in Men With Low HDL-Cholesterol and Desirable LDL-Cholesterol”

This was a double-blind randomized trial comparing 1200 mg per day of gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL-C of 40mg/dl or less, an LDL-C of 140 mg/dl or less, and triglycerides of 300mg/dl or less. The primary outcome was nonfatal myocardial infarction(MI) or death from coronary causes. The midian follow-up was 5.1 years.

There was a risk reduction of 22% in the primary outcome (p=.0006) and 24% risk reduction in the combined endpoint of stroke, MI, and CHD death. The rate of events was reduced by raising HDL-C and lowering triglycerides without lowering LDL-C (N Engl J Med 1999;341:410-418).

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study

Primary Hypothesis:

To determine if drug treatment aimed at raising HDL-cholesterol and lowering triglycerides will reduce the rate of heart attack and death in veterans with coronary heart disease (CHD) and a specific lipid profile characterized by normal levels of LDL-cholesterol and low levels of HDL-cholesterol.

Secondary Hypotheses:

To determine the effect of treatment on total mortality, unstable angina, CABG, PTCA, strokes and PVD, and to determine whether there is an association between changes in plasma lipid levels and outcomes.

Primary Outcomes:

Myocardial infarction (MI), silent MI, and CHD death.

Interventions:

Gemfibrozil (1200 mg per day) versus matching placebo.

Study Abstract:

A double-blind trial was conducted comparing gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg/dL or less, and an LDL cholesterol level of 140 mg/dL or less.

The median follow-up was 5.1 years. At one year, the mean HDL was 6% higher, the mean triglyceride were 31% lower, and the mean total cholesterol was 4% lower in the gemfibrozil group than in the placebo group. LDL levels did not differ between the groups.

A primary event (MI or death) occurred in 275 of the 1267 placebo patients (21.7%) and in 219 of the 1264 gemfibrozil patients (17.3%). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22% (95% confidence interval, 7% to 35%; p=0.006). A 24% relative risk reduction occurred in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (p<0.001).

Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.

The major findings were published in the New England Journal of Medicine in August, 1999. A paper on lipid screening was published in the Journal of Clinical Epidemiology in July, 1999 and one on clinical implications was published in the European Heart Journal. Our cost analysis shows that gemfibrozil therapy is highly cost-effective if not cost-saving, thus providing a strong rationale for incorporating results into clinical practice. A manuscript about lipids as predictors of endpoints was published in JAMA in March, 2001. Another paper on stroke was published in Circulation in June, 2001. Dr. Robins presented data on diabetics in November, 2000 at the AHA. A paper on cost-effectiveness was published in the Archives of Internal Medicine in January 2002. A manuscript on diabetes has been accepted by the Archives of Internal Medicine.

A NHLBI grant for continuing analysis has been funded for two years. Other papers in progress include homocysteines in diabetics, fasting plasma insulin as a predictor of outcome, and the effect of liproprotein subclass particle size on coronary events.

Intervention(s) in this Clinical Trial

• Drug: gemfibrozil

Inclusion criteria:

• 1. male gender
• 2. age 73 or younger
• 3. presence of CHD
• 4. HDL-C le 40 mg/dl
• 5. LDL-C le 140 mg/dl
• 6. triglycerides le 300 mg/dl

Exclusion criteria:

• 1. significant medical illness
• 2. alcohol or substance abuse
• 3. evidence of cholecystitis or cholelithiasis
• 4. ejection fraction of lt 35%
• 5. current use of steroids, estrogens, immunosuppressive agents, oral coagulants, or lipid modifying drug.
• 6. allergic to gemfibrozil or fibric acid
• 7. refused informed consent

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 73 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Department of Veterans Affairs

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00283335

Study ID Number: 363

ClinicalTrials.gov Identifier: NCT00283335

Health Authority: United States: Food and Drug Administration