Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia.
OBJECTIVE
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 N + E/S (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.
Guyton
John R
JR
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. guyto001@mc.duke.edu
Brown
B Greg
BG
Fazio
Sergio
S
Polis
Adam
A
Tomassini
Joanne E
JE
Tershakovec
Andrew M
AM
D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001053:Apolipoproteins / Q000187:drug effects; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D008055:Lipids; D009525:Niacin; D019821:Simvastatin; D000069438:Ezetimibe