Abstract 8824: Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients

Extended-release niacin (ERN) produces improvements across the lipid profile in patients with dyslipidemia, but is underutilized due to flushing, a process primarily mediated by prostaglandin D 2 (PGD 2 ). The PGD 2 receptor antagonist, laropiprant (LRPT), reduces ERN-induced flushing in patients with dyslipidemia. This study tested the hypothesis that, after 20 weeks of the fixed-dose combination ERN/LRPT, patients who continued on ERN/LRPT would have less flushing than patients who had LRPT withdrawn, but continued on ERN alone. After a 2-week placebo run-in, 1152 patients with dyslipidemia were randomized 2:2:1 to one of three daily treatment groups: (1) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg for the remainder of the study; (2) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg from 5 to 20 weeks, then ERN 2g without laropiprant from 21 to 32 weeks; or (3) placebo for the duration of the study. The key endpoints were based on the Global Flushing Severity Score (GFSS) from the previously validated Flushing Symptom Questionnaire: the number of days/week with moderate or greater GFSS ≥4 (primary) and the percentage of patients with maximum GFSS ≥4 (secondary) during the post-withdrawal period of the study (weeks 21 to 32). ERN/LRPT produced significantly less flushing relative to ERN alone during the post-withdrawal period, as measured by the number of days/week with GFSS ≥4 (p<0.001; see fig) and the percentage of patients with maximum GFSS ≥4 (ERN/LRPT: 19.6%; ERN: 48.9%; Placebo: 9.2%). There were fewer drug related adverse experiences during the post-withdrawal period comparing the ERN/LRPT to the ERN treatment groups. In summary, following 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less flushing than patients who had LRPT withdrawn, and continued with ERN alone. This study supports the long-term efficacy (> 24 weeks) of ERN/LRPT in reducing flushing symptoms.