Downloaded from Slide 1 Ezetimibe Coadministered with Atorvastatin in Patients with Hypercholesterolemia and Coronary Heart

Slide 1

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Ezetimibe Coadministered with Atorvastatin in Patients with Hypercholesterolemia and Coronary Heart DiseaseResults of Two Randomized, Double-Blind, Placebo-Controlled Trials

Slide 2


• In CHD patients not at LDL-C goal (<2.60 mmol/L) on atorvastatin, to determine the effects of coadministration of ezetimibe on

– LDL-C goal attainment

– LDL-C reduction

– TC, TG, HDL-C, and other lipid parameters

– Safety profile (adverse experiences, laboratory values, and vital signs)

Study Objectives

CHD=coronary heart disease; LDL-C=low-density lipoprotein cholesterol; TC=total cholesterol; TG=triglycerides; HDL-C=high-density lipoprotein cholesterol

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Study Design

Ezetimibe 10 mg + atorvastatin 10–20 mg (n=220)

Placebo + atorvastatin 10–20 mg (n=230)

–4 weeks Day 0 Week 6

1:1 Randomization

(N=450)

Atorvastatin 10–20 mg+ placebo

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Efficacy Endpoints

• Primary

– Percentage of patients achieving LDL-C goal of ≤2.60 mmol/L (≤100 mg/dL) at study end (week 6)

• Secondary

– Percentage change from baseline in LDL-C, TC, TG, HDL-C, and other lipid parameters

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Baseline Characteristics of Patients

Parameter

Ezetimibe 10 mg + atorvastatin 10–20 mg

(n=220)

Placebo + atorvastatin 10–20 mg

(n=230)

Age (years)Mean±SDRange

63.0±9.339–86

63.4±9.829–89

Gender (% of patients) Male Female

69.530.5

6832

LDL-C (mmol/L)Mean±SDRange

3.18±0.432.3–5.1

3.13±0.402.4–4.3

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Significant Improvement in Goal Attainment with Ezetimibe Coadministered with Atorvastatin

*≤2.60 mmol/L (≤100 mg/dL); **p≤0.001 vs. atorvastatin

0

10

20

30

50

70

90

% P

atie

nts

at

LD

L-C

go

al*

Ezetimibe 10 mg + atorvastatin 10–20 mg (n=219)Placebo + atorvastatin 10–20 mg (n=225)

81%**

22%

80

60

40

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Superior LDL-C–Lowering Efficacy of Ezetimibe Coadministered with Atorvastatin

*Baseline values reflect ≥10 weeks of treatment with atorvastatin alone; **p≤0.001 vs. atorvastatin

–35

–30

–25

–20

–10

0

LS

mea

n %

ch

ang

e fr

om

bas

elin

e*

–31%**

–4%–5

–15


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Ezetimibe Coadministered with Atorvastatin Improved the Lipid Profile in CHD Patients

aExcept for triglycerides, shown as median % change; bBaseline values reflect ≥10 weeks of treatment with atorvastatin alone; cp≤0.001 vs. atorvastatin; dp=0.021 vs. atorvastatin

–25

–20

–10

20

LS

mea

na

% c

han

ge

fro

m b

asel

ineb

–20%c

–2.2%–5

–15

15

10

5

0

3%d

0.1%

HDL-C

–15%c

–0.8%

TGTC


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Ezetimibe Coadministered with Atorvastatin Improved Cholesterol Ratios

LDL-C/HDL-C ratio TC/HDL-C ratio

–35

–15

–5

0

LS

mea

n %

ch

ang

e fr

om

bas

elin

e* –10

–20

–25

–30

*Baseline values reflect ≥10 weeks of treatment with atorvastatin alone; **p≤0.001 vs. atorvastatin

–32%**

–21%**

–3%–1%

Ezetimibe 10 mg + atorvastatin 10–20 mg (n=219)Placebo + atorvastatin 10–20 mg (n=224 for LDL/HDL, n=225 for TC/HDL)

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Drug-Related Clinical Adverse Experiences

Although a patient may have two or more adverse experiences, the patient is counted only once in a category. The same patient may appear in different categories.

% Patients


(n=220)

Placebo +atorvastatin 10–20 mg

(n=230)

Patients with ≥1 drug-related adverse experience

2.3 1.3

Gastrointestinal 0.5 1.3

Musculoskeletal/connective tissue 0.5 0.0

Nervous system 0.9 0.4

Skin/subcutaneous tissue 0.5 0.0

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Laboratory Adverse Experiences

n/N*


(n=220)


(n=230)

Blood bilirubin increased 1/218 0/226

Blood potassium increased 1/1 0**

Creatine kinase increased 0/218 1/227

Fasting blood glucose increased 0/209 1/223

Although a patient may have two or more adverse experiences, the patient is counted only once in a category. The same patient may appear in different categories.

*Number of patients with adverse event/number of patients with postbaseline value; **No associated laboratory test or no patient with postbaselinevalue for the lab test

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Liver and Muscle Safety Profile

ALT=alanine aminotransferase; AST=aspartate aminotransferase; CK=creatine kinase; ULN=upper limit of normal

*Results based on either a single, last measurement ≥3ULN, or a measurement ≥3ULN followed by a measurement <3ULN taken more than three days after last dose of study medication.

% Patients

Parameter

Ezetimibe 10 mg +atorvastatin 10–20 mg

(n=220)


(n=230) p Value

ALT ≥3ULN* 0.5 0.0 NS

AST ≥3ULN* 0.5 0.0 NS

CK ≥3ULN 0.0 0.0 NS

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Summary and Conclusions

• Ezetimibe coadministered with atorvastatin 10 or 20 mg was significantly* more effective than atorvastatin in CHD patients

More patients achieved LDL-C goal (≤2.60 mmol/L)

Greater reduction in LDL-C

Improved lipid profile—TC, TG, HDL-C,** cholesterol ratios

• Ezetimibe coadministered with atorvastatin was well tolerated

Similar to atorvastatin alone

• Treating two sources (production and absorption) of cholesterol ensured more patients achieve their lipid lowering goals

*p≤0.001; **p=0.021

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References

• Please see notes page.

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Ezetimibe Coadministered with Atorvastatin in Patients with Hypercholesterolemia and Coronary Heart Disease

Before prescribing, please consult the manufacturers’ prescribing information.

MSP does not recommend the use of any productin any different manner than as described

in the prescribing information.

Copyright © 2005 MSP Singapore Company, LLC. All rights reserved.3-08 EZT 2005-W-166205-SS Printed in USA

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