Although low levels of high-density lipoprotein (HDL) cholesterol are usually accompanied by other lipid abnormalities, low HDL levels in isolation may signal a risk of premature coronary artery disease in nonobese, nonsmoking patients who exercise regularly. Zema studied the efficacy and safety of gemfibrozil and niacin, alone and in combination, in increasing low HDL levels in patients with coronary artery disease or peripheral artery disease and no other lipid abnormalities.

The 23 patients (22 men and one woman) in the open-label crossover study had HDL levels less than 40 mg per dL (1.05 mmol per L). Twenty-two had coronary artery disease, and one had peripheral vascular disease. They were randomly assigned to receive 600 mg of gemfibrozil twice daily, 100 to 250 mg of niacin three times daily or a combination of 600 mg of gemfibrozil twice daily and the maximal tolerated dosage of niacin. Patients received maximal dosages of the agents for three months, if tolerated, and then crossed over to the other treatment arm.

In the 14 patients who were able to tolerate all three treatments, the mean HDL cholesterol level increased by 15 percent with gemfibrozil, by 35 percent with niacin and by 45 percent with the combination of gemfibrozil and niacin. Approximately 40 percent of the patients could not tolerate one or both of the drugs. The main side effects of gemfibrozil were gastrointestinal. Flushing was the main side effect of niacin.

The author concludes that drug therapy with gemfibrozil, niacin or a combination of the two can increase isolated low HDL levels. The best results occurred with the combination of gemfibrozil and niacin.