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

• Published in: The American journal of cardiology Vol. 101; no. 5; pp. 625 - 630
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01-03-2008
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Creatine Kinase - blood; Cross-Over Studies; Delayed-Action Preparations; Dermatology; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyslipidemias - drug therapy; Female; Flushing - chemically induced; Flushing - prevention & control; Humans; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - adverse effects; Indoles - administration & dosage; Male; Medical sciences; Middle Aged; Niacin - administration & dosage; Niacin - adverse effects; Receptors, Immunologic - antagonists & inhibitors; Receptors, Prostaglandin - antagonists & inhibitors; Skin involvement in other diseases. Miscellaneous. General aspects; Vascular disorders of the skin; Human; Laropiprant; Skin disease; Nicotinic acid; Metabolic diseases; Cardiovascular disease; Lipids; Hot flush; Vascular disease; Circulatory system; Cardiology; Dyslipemia; Erythema
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2007.10.023

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.