Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial

JAMA. 2001 Mar 28;285(12):1585-91. doi: 10.1001/jama.285.12.1585.


Context: A low plasma level of high-density lipoprotein cholesterol (HDL-C) is a major risk factor for coronary heart disease (CHD). A secondary prevention study, the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT), demonstrated that CHD events were significantly reduced during a median follow-up of 5.1 years by treating patients with the fibric acid derivative gemfibrozil when the predominant lipid abnormality was low HDL-C.

Objective: To determine if the reduction in major CHD events with gemfibrozil in VA-HIT could be attributed to changes in major plasma lipid levels.

Design: Multicenter, randomized, double-blind, placebo-controlled trial conducted from September 1991 to August 1998.

Setting: The Department of Veterans Affairs Cooperative Studies Program, in which 20 VA medical centers were participating sites.

Participants: A total of 2531 men with a history of CHD who had low HDL-C levels (mean, 32 mg/dL [0.83 mmol/L] ) and low low-density lipoprotein cholesterol (LDL-C) levels (mean, 111 mg/dL [2.88 mmol/L]).

Intervention: Participants were randomly assigned to receive gemfibrozil, 1200 mg/d (n = 1264), or matching placebo (n = 1267).

Main outcome measure: Relation of lipid levels at baseline and averaged during the first 18 months of gemfibrozil treatment with the combined incidence of nonfatal myocardial infarction and CHD death.

Results: Concentrations of HDL-C were inversely related to CHD events. Multivariable Cox proportional hazards analysis showed that CHD events were reduced by 11% with gemfibrozil for every 5-mg/dL (0.13-mmol/L) increase in HDL-C (P =.02). Events were reduced even further with gemfibrozil beyond that explained by increases in HDL-C values, particularly in the second through fourth quintiles of HDL-C values during treatment. During gemfibrozil treatment, only the increase in HDL-C significantly predicted a lower risk of CHD events; by multivariable analysis, neither triglyceride nor LDL-C levels at baseline or during the trial predicted CHD events.

Conclusions: Concentrations of HDL-C achieved with gemfibrozil treatment predicted a significant reduction in CHD events in patients with low HDL-C levels. However, the change in HDL-C levels only partially explained the beneficial effect of gemfibrozil.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Double-Blind Method
  • Gemfibrozil / therapeutic use*
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Lipids / blood
  • Male
  • Multivariate Analysis
  • Myocardial Infarction
  • Proportional Hazards Models
  • Survival Analysis


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Lipids
  • Gemfibrozil