The VA HDL Intervention Trial
Information source: Department of Veterans Affairs
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Coronary Heart Disease
Intervention: gemfibrozil (Drug)
Phase: Phase 3
Sponsored by: Department of Veterans Affairs
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).
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
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study
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
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.
Myocardial infarction (MI), silent MI, and CHD death.
Gemfibrozil (1200 mg per day) versus matching placebo.
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
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.
Minimum age: N/A.
Maximum age: 73 Years.
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
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
Locations and Contacts
Starting date: June 1991
Ending date: September 1998
Last updated: January 26, 2006