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CLINICAL RESEARCH: LIPIDS AND VASCULAR DISEASE

Lipid-Altering Efficacy and Safety of Ezetimibe/Simvastatin Coadministered With Extended-Release Niacin in Patients With Type IIa or Type IIb Hyperlipidemia

John R. Guyton, MD^_*,_*, B. Greg Brown, MD, PhD, Sergio Fazio, MD, PhD, Adam Polis, MA, Joanne E. Tomassini, PhD and Andrew M. Tershakovec, MD, MPH

^_* Department of Medicine, Duke University Medical Center, Durham, North Carolina
Department of Medicine, Division of Cardiology, University of Washington, Seattle, Washington
Vanderbilt Lipid Laboratory, Vanderbilt University Medical Center, Nashville, Tennessee
Clinical and Quantitative Sciences, Merck & Co., Inc., North Wales, Pennsylvania.

Manuscript received December 4, 2007; revised manuscript received February 19, 2008, accepted March 4, 2008.

^_* Reprint requests and correspondence: Dr. John R. Guyton, Department of Medicine, Duke University Medical Center, Trent Drive, Durham, North Carolina 27710. (Email: guyto001{at}mc.duke.edu).

Objectives: This study evaluated the safety and lipid-altering efficacy of ezetimibe/simvastatin (E/S) coadministered with extended-release niacin (N) in patients with type IIa or IIb hyperlipidemia.

Background: Current guidelines recommend consideration of combination drug therapy to achieve optimal low-density lipoprotein cholesterol (LDL-C) lowering and broader lipid-altering effects when treating hypercholesterolemic patients at high risk for atherosclerotic cardiovascular events.

Methods: In this 24-week multicenter, randomized, double-blind study, 1,220 type IIa or IIb hyperlipidemic patients were 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). Changes from baseline in LDL-C (primary) and other secondary variables were assessed in the completers and modified intent-to-treat populations.

Results: Coadministered E/S with N resulted in significantly greater reductions in LDL-C, non–high-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and lipid/lipoprotein ratios, compared with either agent alone (p < 0.001). The combination increased levels of apolipoprotein A-I and high-density lipoprotein cholesterol significantly more than E/S (p < 0.001), and reduced high-sensitivity C-reactive protein levels significantly more than N (p = 0.005). A significantly greater percentage of patients discontinued the study in the N (25.0%) and E/S + N (23.3%) groups, compared with E/S (9.6%, p < 0.001) because of clinical adverse experiences (primarily flushing). Incidences of other clinical and laboratory adverse experiences (liver-, muscle-, and gastrointestinal-related) were similar for all groups.

Conclusions: Combination treatment with E/S plus N showed superior lipid-altering efficacy compared with N or E/S in type IIa or IIb hyperlipidemia patients and was generally well tolerated aside from N-associated flushing. This combination offers an effective, broad, lipid-altering therapy with improvements in lipid effects beyond LDL-C in these patients. (To Evaluate Ezetimibe/Simvastatin and Niacin [Extended Release Tablet] in Patients With High Cholesterol; NCT00271817)

Abbreviations and Acronyms   AE = adverse experience   Apo = apolipoprotein   CHD = coronary heart disease   CK = creatine kinase   E/S = ezetimibe/simvastatin   HDL-C = high-density lipoprotein cholesterol   hsCRP = high-sensitivity C-reactive protein   LDL-C = low-density lipoprotein cholesterol   LOCF = last observation carried forward   mITT = modified intent-to-treat   N = extended-release niacin   TC = total cholesterol   ULN = upper limit of normal