Details

Autor(en) / Beteiligte

• Paolini, John F., MD, PhD
• Mitchel, Yale B., MD
• Reyes, Robert, BA
• Kher, Uma, PhD
• Lai, Eseng, MD, PhD
• Watson, Douglas J., PhD, MSPH
• Norquist, Josephine M., MS
• Meehan, Alan G., PhD
• Bays, Harold E., MD
• Davidson, Michael, MD
• Ballantyne, Christie M., MD

Titel

Effects of Laropiprant on Nicotinic Acid-Induced Flushing in Patients With Dyslipidemia

Ist Teil von

• The American journal of cardiology, 2008-03, Vol.101 (5), p.625-630

Ort / Verlag

New York, NY: Elsevier

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• Niacin (nicotinic acid) is not optimally used mainly because of flushing, a process mediated primarily by prostaglandin D2 , which leads to poor patient compliance and suboptimal dosing. This phase II dose-ranging study was designed to assess whether the prostaglandin D2 receptor 1 antagonist laropiprant (LRPT; MK-0524) would (1) reduce extended-release niacin (ERN)–induced flushing in dyslipidemic patients and (2) support a novel accelerated ERN dosing paradigm: initiating ERN at 1 g and advancing rapidly to 2 g. In part A of the study, 154 dyslipidemic patients were randomized to LRPT 150 mg/day or placebo in a 9-week, 2-period crossover study. Patients who completed part A (n = 122) entered part B (after a 2-week washout), together with additional patients who entered part B directly (n = 290). Part B patients were randomized to placebo, ERN 1 g (Niaspan, no previous titration), or ERN 1 g coadministered with LRPT 18.75, 37.5, 75, or 150 mg for 4 weeks, with doubling of the respective doses for the remaining 4 weeks. Patients treated with LRPT plus ERN experienced significantly less ERN-induced flushing than those treated with ERN alone during the initiation of treatment (ERN 1 g, week 1) and the maintenance treatment (ERN 1 to 2 g, weeks 2 to 8). All doses of LRPT were maximally effective in inhibiting niacin-induced flushing. LRPT did not alter the beneficial lipid effects of ERN. LRPT plus ERN was well tolerated. In conclusion, the significant reduction in ERN-induced flushing provided by LRPT plus ERN supports an accelerated ERN dose-advancement paradigm to achieve rapidly a 2-g dose in dyslipidemic patients.