Objective: To evaluate the safety and efficacy of controlled-release niacin in patients with hyperlipoproteinemia.
Design: A retrospective cohort study.
Setting: A Department of Veterans Affairs Medical Center.
Patients: A consecutive sample of 969 predominantly elderly male veterans treated for dyslipoproteinemia with controlled-release niacin between October 1988 and October 1991.
Main Outcome Measures: Primary outcomes were lipid levels and lipoprotein cholesterol response, alterations in levels of hepatic enzymes and blood chemistry test results, and characterization of niacin-induced hepatotoxicity abstracted from the patient's medical, laboratory, and pharmacy records.
Results: 93% (896 of 969) of the cohort was evaluable. Patients (age, 61.7 years [9.4 years], mean [SD]) were treated for 1 to 36 months (13.0 months [9.7 months]) with an average maintenance dose of 1.67 g/d (0.8 g/d). Niacin was discontinued in 48.5% (435 of 896) of the patients primarily because of adverse effects. Poor glycemic control led to discontinuation in 40.6% (43 of 106) of the patients with diabetes mellitus. The lipoprotein response was dose-related and favorable (levels of total cholesterol, −19.1%;low-density lipoprotein cholesterol, −24.0%;high-density lipoprotein cholesterol, +5.7%; and triglycerides, −32.5%).Statistically but not clinically meaningful dose-related increases were seen in levels of liver enzymes and serum glucose (aspartate aminotransferase, +29%; alanine aminotransferase, +23%; alkaline phosphatase, +25%; and glucose, +7%; P = 0.0001). Twenty of 896 (2.2%) and 42 of 896 (4.7%) patients met biochemical criteria for probable and for possible or probable niacin-induced hepatotoxicity, respectively. Predisposing factors included high dose, alcohol use, preexisting liver disease, and concurrent oral sulfonylurea therapy.
Conclusions: Controlled-release niacin is effective in treating dyslipoproteinemia in selected middle-aged and elderly veterans, but approximately one half of patients discontinued the drug because of adverse effects or other causes including noncompliance. Niacin should be avoided in patients with hepatic dysfunction or a history of liver disease, patients with diabetes mellitus, and patients who abuse alcohol. Because controlled-release niacin seems to be more potent than crystalline niacin, product substitution without dose adjustment should be avoided.