A COMPARISON OF THE EFFICACY AND TOXIC EFFECTS OF SUSTAINED-RELEASE VS IMMEDIATE-RELEASE NIACIN IN HYPERCHOLESTEROLEMIC PATIENTS

Objective.-To compare escalating doses of immediate-release (IR) and s ustained-release (SR) niacin for effectiveness in reducing levels of l ow-density lipoprotein cholesterol and triglycerides and increasing le vels of high-density lipoprotein cholesterol, and for the occurrence o f adverse reactions, especially hepatotoxicity. Design.-Randomized, do uble-blind, parallel comparison of IR and SR niacin administered seque ntially at 500, 1000, 1500, 2000, and 3000 mg/d, each for 6 weeks. Set ting.-Cholesterol research center. Patients.-Forty-six adults, 23 in e ach group, with low-density lipoprotein cholesterol levels greater tha n 4.14 mmol/l (160 mg/dL) after 1 month of a step 1 National Cholester ol Education Program diet. Outcome Measures.-Fourteen-hour fasting lip id and lipoprotein cholesterol levels, results of clinical laboratory tests, a symptom questionnaire, and withdrawal rates. Results.-The SR niacin lowered low-density lipoprotein cholesterol levels significantl y more than IR niacin did at the dosage of 1500 mg/d and above, while IR niacin increased high-density lipoprotein cholesterol levels signif icantly more than SR niacin did at all dosage levels. The reduction in triglyceride levels was similar with IR and SR niacin. Nine (39%) of the 23 patients assigned to the IR dosage form withdrew before complet ing the 3000-mg daily dose; the most common reasons for withdrawal wer e vasodilatory symptoms, fatigue, and acanthosis nigricans. Eighteen ( 78%) of the 23 patients assigned to the SR dosage form withdrew before completing the 3000-mg daily dose; the most common reasons for withdr awal were gastrointestinal tract symptoms, fatigue, and increases in l evels of liver aminotransferases, often with symptoms of hepatic dysfu nction. None of the patients taking IR niacin developed hepatoxic effe cts, while 12 (52%) of the 23 patients taking SR niacin did. Conclusio n.-The SR form of niacin is hepatotoxic and should be restricted from use. The IR niacin is preferred for the management of hypercholesterol emia but can also cause significant adverse effects and should be give n only to patients who can be carefully monitored by experienced healt h professionals.