Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial - VA-HIT

Description:

Gemfibrozil versus placebo for secondary prevention of coronary heart disease (CHD)

Hypothesis:

To determine if the fibric derivative can reduce CHD death and myocardial infarction (MI) in patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol.

Study Design

Study Design:

Patients Screened: Not reported
Patients Enrolled: 2,531
NYHA Class: 8% with history of CHF
Mean Follow Up: Median 5.1 years
Mean Patient Age: Mean 64 years
Female: 0
Mean Ejection Fraction: Not reported

Patient Populations:

Documented CHD (prior MI or coronary revascularization, a history of angina with documented myocardial ischemia, or an angiogram positive for coronary artery disease); low HDL (≤40 mg/dl); LDL (≤140 mg/dl); and triglycerides (≤300 mg/dl)

Exclusions:

Age 74 or greater and serious coexisting conditions

Primary Endpoints:

Nonfatal MI or CHD death (sudden death, death due to MI, death due to congestive heart failure [CHF], and death as a complication of invasive cardiac procedures)

Secondary Endpoints:

Lipid levels, all-cause mortality, coronary revascularization, hospitalization for unstable angina, total stroke (both reported and as adjudicated by blinded committee), transient ischemic attacks, and carotid endarterectomy

Drug/Procedures Used:

Gemfibrozil (1200 mg per day) with placebo

Concomitant Medications:

Aspirin (82%), nitrates (46%), calcium channel blockers(53%), beta-blockers (43%), and angiotensin-converting enzyme inhibitors (21%)

Principal Findings:

At one year, gemfibrozil administration was associated with a 6% higher mean HDL cholesterol level, 31% lower mean triglyceride level, and 4% lower mean total cholesterol level compared to placebo. Low-density lipoprotein (LDL) cholesterol levels did not differ significantly between the two groups.

Gemfibrozil administration was associated with a significant 22% relative reduction in the risk of CHD death or MI compared to placebo (17.3% vs. 21.7%, p=0.006). Gemfibrozil administration was associated with a 24% relative reduction in the composite endpoint of CHD death, nonfatal MI, and stroke (p<0.001).

Of note, the beneficial effect of gemfibrozil did not become apparent until approximately two years after randomization. There were no significant differences between the groups in the rates of coronary revascularization, hospitalization for unstable angina, all-cause mortality, and cancer.

Interpretation:

Gemfibrozil therapy was associated with a significant reduction in CHD death and major cardiovascular events among patients whose primary lipid abnormality was a low HDL cholesterol level. This is the first major randomized trial demonstrating benefit of lipid-lowering therapy in CHD patients with both low HDL and low LDL, and suggests that there is a clinical benefit to raising HDL and lowering triglycerides with modest lowering of LDL.

These findings are most applicable to the group of CHD patients with LDL less than 130, more than half of whom have low levels of HDL cholesterol. VA-HIT enrolled patients with lower levels of HDL and LDL compared to other recent major secondary prevention trials of lipid-lowering therapy, including 4S, LIPID, and CARE.

References:

Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410-8.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Neoplasms, Cholesterol, LDL, Gemfibrozil, Cholesterol, HDL, Triglycerides


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