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

Abstract

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.

32 Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

“…190 -192 Combination of niacin with laropiprant, an inhibitor of the prostaglandin D 2 receptor, 193 significantly reduced but did not abolish flushing, the main tolerability issue. Among patients with T2DM, transient impairment of glucose control was reported (median increase in HbA 1C 0.3% over 12 weeks), 194,195 consistent with known effects with niacin. 188,189 Emerging evidence suggests that statin plus niacin can reduce progression of atherosclerosis in high-risk patients, including those with low LDL-C, as in the Oxford Niaspan trial 182 (Supplementary material online, Table S1).…”

Extended-release niacin with laropiprant: a review on efficacy, clinical effectiveness and safety

“…Adding ERN/LRPT to statin has been shown to have a greater effect than doubling statin dose in improving lipid profile (LDL-C, -10 vs -5.5%; HDL-C, 15.8 vs 0.2%; TGL, -17.6 vs -4%; apoB, -10.7 vs -2.4%; apoA1, 6.9 vs 1% and Lp (a), -18.2 vs 0%; p < 0.001 for all) [102]. In the same study, [104].…”

“…Approximately 6000 patients have participated in many studies focusing on safety of ERN/LRPT combination compared with ERN, statins or placebo [50,85,101,102,121]. The outcomes suggest that the combination of ERN and LRPT is as safe as ERN alone [55] but there is no long-term data on the safety of LRPT.…”

Consistency of Extended-Release Niacin/Laropiprant Effects on Lp(a), ApoB, non-HDL-C, Apo A1, and ApoB/ApoA1 Ratio Across Patient Subgroups

“…Prior studies have shown that ERN LRPT improves key lipid parameters associated with increased CHD risk in patients with primary hypercholesterolemia or mixed dyslipidemia. [12][13][14][15] CHD risk may vary among different patient subgroups, including sex, race, and age. [16] CHD risk may also differ among patients based on their lipid levels, use of statin therapy, CHD risk category, and type of hyperlipidemia.…”