brand logo

Am Fam Physician. 1999;60(8):2417-2418

Several studies have now established the benefit of decreasing low-density lipoprotein (LDL) cholesterol levels in persons with established heart disease. However, about 40 percent of patients with coronary artery disease have normal LDL cholesterol levels but decreased levels of high-density lipoprotein (HDL) cholesterol levels. Observational studies have found that low HDL levels are strongly associated with a higher risk of coronary heart disease. Rubins and colleagues reported the results of the Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) that attempted to determine if increasing HDL cholesterol levels and decreasing triglyceride levels would decrease the incidence of death from coronary heart disease and nonfatal myocardial infarction in men with coronary artery disease.

Patients were enrolled from 20 different Veterans Affairs medical centers throughout the United States. Entry criteria included a history of coronary artery disease based on a prior myocardial infarction, angina corroborated by objective evidence of ischemia, coronary revascularization or angiographic documentation of at least 50 percent stenosis of one or more major epicardial arteries. Other criteria included age less than 74 years, an HDL cholesterol level of 40 mg per dL (1 mmol per L) or less, a triglyceride level of 300 mg per dL (3.4 mmol per liter) or less and an LDL cholesterol level of less than 140 mg per dL (3.6 mmol per L). The patients were randomized to receive either 1,200 mg per day of slow-release gemfibrozil or placebo. After the manufacturer discontinued the slow-release formulation, study participants received a dosage of 600 mg of regular gemfibrozil twice daily or matching placebo. No changes were seen in lipid levels after this substitution. Patients were seen one month after randomization, then every three months for the remainder of the study. A fasting lipid panel was performed every six months for the first one half of the study and then yearly. All patients were encouraged to follow the American Heart Association Step 1 diet and an exercise program. The primary outcome was combined incidence of myocardial infarction or death from coronary artery disease. Secondary outcomes included death from any cause, stroke, transient ischemic attack, carotid endarterectomy, coronary revascularization and hospitalization for unstable angina.

During the first two and one half years of the study, 2,531 men were enrolled. All patients were subsequently followed for a median of 5.1 years. The mean age of participants was 64 years, and 90 percent were white. More than 50 percent of participants had hypertension, and 25 percent had diabetes. The mean HDL cholesterol level at entry was 32 mg per dL (0.8 mmol per L), and the mean LDL cholesterol level was 112 mg per dL (2.9 mmol per L). After the first year of gemfibrozil therapy, mean HDL levels were 6 percent higher in the treatment group than in the placebo group, and mean total cholesterol levels were 4 percent lower.

The primary outcome revealed that 275 patients in the placebo group (compared with 219 in the gemfibrozil group) died from coronary heart disease or had a nonfatal myocardial infarction. This difference translated to a relative risk reduction of 22 percent in death from coronary heart disease and 23 percent in nonfatal myocardial infarction. This benefit was not observed until about two years after randomization. Assessment of stroke revealed that 76 patients in the placebo group and 58 in the treatment group suffered a neurologic event. This amounted to a relative risk reduction of 25 percent in the treatment group. Also observed was a statistically significant decrease in the risk of transient ischemic attack and carotid endarterectomy. No differences in the rates of coronary revascularization or hospitalization for unstable angina were noted. The most commonly observed adverse event was dyspepsia, which occurred in 40 percent of the gemfibrozil patients but also in 34 percent of patients receiving placebo. No differences in the number of patients with elevated creatinine kinase or aspartate aminotransferase levels were found.

The authors conclude that gemfibrozil therapy reduces the risk of death and nonfatal myocardial infarction in patients with known coronary disease and low HDL cholesterol levels.

editor's note: This study adds further support to several other secondary prevention studies that have used statin medications to lower LDL cholesterol levels in patients with established heart disease. In this study, the absolute risk reduction in death from coronary heart disease or myocardial infarction was 4.4 percent. This reduction translates into 23 patients who would need to be treated with gemfibrozil for five years to prevent one event. This number needed to treat compares favorably with two of the major statin trials, where the number of patients needed to treat ranged from 28 to 33.—j.t.k.

Continue Reading

More in AFP

Copyright © 1999 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See for copyright questions and/or permission requests.