Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. Robins SJ， Collins D， Wittes JT， Papademetriou V， Deedwania PC， Schaefer EJ， McNamara JR， Kashyap ML， Hershman JM， Wexler LF， Rubins HB; VA-HIT Study Group. Veterans Affairs High-Density Lipoprotein Intervention Trial. Department of Medicine， Boston University School of Medicine， 88 E Newton St， Boston， MA 02118， USA. sjrobins@bu.edu
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.