Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia

Summary Background: Co‐administration of niacin with statin offers the potential for additional lipid management and cardiovascular risk reduction. However, niacin is underutilised because of the side effects of flushing, mediated primarily by prostaglandin D2 (PGD2). A combination tablet containing extended‐release niacin and laropiprant (ERN/LRPT), a PGD2 receptor (DP1) antagonist, offers improved tolerability. This study assessed the efficacy and safety of ERN/LRPT added to statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia who were not at their National Cholesterol Education Program Adult Treatment Panel III low‐density lipoprotein cholesterol (LDL‐C) goal based on their coronary heart disease risk category (high, moderate or low). Methods: After a 2‐ to 6‐week run‐in statin (simvastatin 10 or 20 mg or atorvastatin 10 mg) period, 1216 patients were randomised equally to one of two treatment groups in a double‐blind fashion: group 1 received ERN/LRPT (1 g) plus the run‐in statin dose and advanced to ERN/LRPT (2 g) after 4 weeks for an additional 8 weeks, with no adjustments to the run‐in statin dose; group 2 received simvastatin or atorvastatin at twice their run‐in statin dose and remained on this stable dose for 12 weeks. Results: ERN/LRPT added to statin (pooled across statin and statin dose) significantly improved key lipid parameters vs. the doubled statin dose (pooled): the between‐treatment group difference in least squares mean per cent change [95% confidence interval (CI)] from baseline to week 12 in LDL‐C (primary end‐point) was −4.5% (−7.7, −1.3) and in high‐density lipoprotein cholesterol (HDL‐C) was 15.6% (13.4, 17.9) and in median per cent change for triglyceride (TG) was −15.4% (−19.2, −11.7). Treatment‐related adverse experiences (AEs) related to flushing, pruritis, rash, gastrointestinal upset and elevations in liver transaminases and fasting serum glucose occurred more frequently with ERN/LRPT added to statin vs. statin dose doubled. Conclusions: The addition of ERN/LRPT to ongoing statin treatment produced significantly improved lipid‐modifying benefits on LDL‐C, HDL‐C and TG and all other lipid parameters compared with doubling the statin dose in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The types of AEs that occurred at a greater frequency in the ERN/LRPT group were those typically associated with niacin.