EFFICACY AND SAFETY OF CONTROLLED-RELEASE NIACIN IN DYSLIPOPROTEINEMIC VETERANS

Objective: To evaluate the safety and efficacy of controlled-release n iacin in patients with hyperlipoproteinemia. Design: A retrospective c ohort study. Setting: A Department of Veterans Affairs Medical Center. Patients: A consecutive sample of 969 predominantly elderly male vete rans treated for dyslipoproteinemia with controlled-release niacin bet ween October 1988 and October 1991. Main Outcome Measures: Primary out comes were lipid levels and lipoprotein cholesterol response, alterati ons 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% (89 6 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 m onths]) 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 beca use of adverse effects. Poor glycemic control led to discontinuation i n 40.6% (43 of 106) of the patients with diabetes mellitus. The lipopr otein response was dose-related and favorable (levels of total cholest erol, -19.10/b; low-density lipoprotein cholesterol, -24.0%; high-dens ity lipoprotein cholesterol, +5.7%; and triglycerides, -32.5%). Statis tically but not clinically meaningful dose-related increases were seen in levels of liver enzymes and serum glucose (aspartate aminotransfer ase, +29%; alanine aminotransferase, +23%; alkaline phosphatase, +25%; and glucose, +7%; P= 0.0001). Twenty of 896 (12.2%) and 42 of 896 (4. 7%) patients met biochemical criteria for probable and for possible or probable niacin-induced hepatotoxicity, respectively. Predisposing fa ctors 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 disc ontinued the drug because of adverse effects or other causes including noncompliance. Niacin should be avoided in patients with hepatic dysf unction or a history of liver disease, patients with diabetes mellitus , and patients who abuse alcohol. Because controlled-release niacin se ems to be more potent than crystalline niacin, product substitution wi thout dose adjustment should be avoided.