Clinical trial experience with extended-release niacin (Niaspan): Dose-escalation study

Niacin is a useful lipid-modifying drug because it (1) decreases low-densit y lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and lipo protein(a), and (2) raises high-density lipoprotein (HDL) cholesterol. Its use tends to be limited by side effects and inconvenient dosing regimens. T he availability of an extended-release preparation (Niaspan-which has safet y and efficacy similar to immediate-release niacin but which can be given o nce a day) provides an opportunity to increase the use of this effective li pid-modifying agent. To study the safety and efficacy of escalating doses o f extended-release niacin, hyperlipidemic patients were randomly assigned t o placebo or Niaspan. A forced dose-titration was done with the dosage incr easing by 500 mg every 4 weeks to a maximum of 3,000 mg/day. Niaspan showed dose-related changes in total, LDL, and HDL cholesterol levels, triglyceri des, cholesterol/HDL ratio, and lipoprotein(a). At a dosage of 2,000 mg/day , total cholesterol decreased by 12.1%, LDL cholesterol by 16.7%, triglycer ides by 34.5%, and lipoprotein(a) by 23.6%; HDL cholesterol increased by 25 .8%. Flushing was the most commonly reported side effect flushing episodes tended to decrease with time despite an increasing dose of niacin. Of the r eported side effects, only pruritus and rash were significantly different b etween the 2 groups. Aspartate aminotransferase, lactate dehydrogenase, and uric acid increased in a dose-dependent fashion, but fasting blood sugar i ncreased by about 5% across most dosages. Two subjects had aspartate aminot ransferase levels greater than twice the upper limit of normal, but there w ere no subjects in whom transaminases increased to 3 rimes the upper limit of normal. Women tended to have a greater LDL cholesterol response to the m edication and also experienced more side effects, especially at higher dosa ges. Thus, the use of lower dosages of niacin may be desirable in women. Th e results of this dose-escalation study show beneficial effects of Niaspan on the entire lipid profile. Ar the maximum recommended dosage of 2,000 mg/ day, all lipid and lipoprotein levels changed in desirable directions. Side effects (other than flushing) and blood chemistries were comparable to tho se seen with immediate-release niacin. (C) 1998 by Excerpta Medico, Inc.