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, B. Greg Brown, Sergio Fazio, Adam Polis, Joanne E. Tomassini, Andrew M. Tershakovec

Research output: Contribution to journalArticle

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Abstract

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 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; NCT00271817).

Original languageEnglish (US)
Pages (from-to)1564-1572
Number of pages9
JournalJournal of the American College of Cardiology
Volume51
Issue number16
DOIs
StatePublished - Apr 22 2008
Externally publishedYes

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Simvastatin
Niacin
Hyperlipidemias
Lipids
Safety
LDL Cholesterol
Apolipoprotein A-I
Apolipoproteins B
Ezetimibe
Combination Drug Therapy
Double-Blind Method
C-Reactive Protein
HDL Cholesterol
Tablets
Lipoproteins
Triglycerides
Therapeutics
Cholesterol
Guidelines
Muscles

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Lipid-Altering Efficacy and Safety of Ezetimibe/Simvastatin Coadministered With Extended-Release Niacin in Patients With Type IIa or Type IIb Hyperlipidemia. / Guyton, John R.; Brown, B. Greg; Fazio, Sergio; Polis, Adam; Tomassini, Joanne E.; Tershakovec, Andrew M.

In: Journal of the American College of Cardiology, Vol. 51, No. 16, 22.04.2008, p. 1564-1572.

Research output: Contribution to journalArticle

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abstract = "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 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; NCT00271817).",
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T1 - Lipid-Altering Efficacy and Safety of Ezetimibe/Simvastatin Coadministered With Extended-Release Niacin in Patients With Type IIa or Type IIb Hyperlipidemia

AU - Guyton, John R.

AU - Brown, B. Greg

AU - Fazio, Sergio

AU - Polis, Adam

AU - Tomassini, Joanne E.

AU - Tershakovec, Andrew M.

PY - 2008/4/22

Y1 - 2008/4/22

N2 - 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 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; NCT00271817).

AB - 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 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; NCT00271817).

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