Changes in Lipoprotein Particle Number With Ezetimibe/Simvastatin Coadministered With Extended‐Release Niacin in Hyperlipidemic Patients

BACKGROUND: Combination therapy with ezetimibe/simvastatin (E/S) and extended‐release niacin (N) has been reported to be safe and efficacious in concomitantly reducing low‐density lipoprotein cholesterol and increasing high‐density lipoprotein cholesterol in hyperlipidemic patients at high risk for atherosclerotic cardiovascular events. This analysis evaluated the effect of E/S coadministered with N on low‐density lipoprotein particle number (LDL‐P) and high‐density lipoprotein particle number (HDL‐P) as assessed by nuclear magnetic resonance (NMR) spectroscopy in patients with type IIa or IIb hyperlipidemia. METHODS AND RESULTS: This was an analysis of a previously reported 24‐week randomized, double‐blind study in type IIa/IIb hyperlipidemic patients randomized to treatment with E/S (10/20 mg/day)+N (titrated to 2 g/day) or N (titrated to 2 g/day) or E/S (10/20 mg/day). Samples from a subset of patients (577 of 1220) were available for post hoc analysis of LDL‐P and HDL‐P by NMR spectroscopy. Increases in HDL‐P (+16.2%) and decreases in LDL‐P (−47.7%) were significantly greater with E/S+N compared with N (+9.8% for HDL‐P and −21.5% for LDL‐P) and E/S (+12.8% for HDL‐P and −36.8% for LDL‐P). In tertile analyses, those with the lowest baseline HDL‐P had the greatest percent increase in HDL‐P (N, 18.4/7.9/2.1; E/S, 19.3/12.2/5.3; and E/S+N, 26.9/13.8/6.9; all P<0.001). Individuals in the highest tertile of LDL‐P had the greatest percent reduction in LDL‐P (N, 18.3/23.1/24.6; E/S, 29.7/38.3/41.8; and E/S+N, 44.3/49.0/50.5; all P<0.001). CONCLUSIONS: These results suggest that E/S+N improves lipoprotein particle number, consistent with its lipid‐modifying benefits in type IIa or IIb hyperlipidemia patients and may exert the greatest effect in those with high LDL‐P and low HDL‐P at baseline. CLINICAL TRIAL REGISTRATION: URL: Clinicaltrials.gov Identifier: NCT00271817