1. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 1 Ezetimibe Coadministered with Atorvastatin in Patients with Hypercholesterolemia and Coronary Heart Disease Results of Two Randomized, Double-Blind, Placebo- Controlled Trials

2. Downloaded from www.ezetrol.aewww.ezetrol.ae 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

3. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 3 Study Design Ezetimibe 10 mg + atorvastatin 10–20 mg (n=220) Placebo + atorvastatin 10–20 mg (n=230) –4 weeksDay 0 Week 6 1:1 Randomization (N=450) Atorvastatin 10–20 mg + placebo

4. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 4 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

5. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 5 Baseline Characteristics of Patients Parameter Ezetimibe 10 mg + atorvastatin 10–20 mg (n=220) Placebo + atorvastatin 10–20 mg (n=230) Age (years) Mean±SD Range 63.0±9.3 39–86 63.4±9.8 29–89 Gender (% of patients) Male Female 69.5 30.5 68 32 LDL-C (mmol/L) Mean±SD Range 3.18±0.43 2.3–5.1 3.13±0.40 2.4–4.3

6. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 6 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 % Patients at LDL-C goal* Ezetimibe 10 mg + atorvastatin 10–20 mg (n=219) Placebo + atorvastatin 10–20 mg (n=225) 81%** 22% 80 60 40

7. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 7 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 mean % change from baseline* –31%** –4% –5 –15 Ezetimibe 10 mg + atorvastatin 10–20 mg (n=219) Placebo + atorvastatin 10–20 mg (n=224)

8. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 8 Ezetimibe Coadministered with Atorvastatin Improved the Lipid Profile in CHD Patients a Except for triglycerides, shown as median % change; b Baseline values reflect ≥10 weeks of treatment with atorvastatin alone; c p≤0.001 vs. atorvastatin; d p=0.021 vs. atorvastatin –25 –20 –10 20 LS mean a % change from baseline b –20% c –2.2% –5 –15 15 10 5 0 3% d 0.1% HDL-C –15% c –0.8% TGTC Ezetimibe 10 mg + atorvastatin 10–20 mg (n=219) Placebo + atorvastatin 10–20 mg (n=225)

9. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 9 Ezetimibe Coadministered with Atorvastatin Improved Cholesterol Ratios LDL-C/HDL-C ratioTC/HDL-C ratio –35 –15 –5 0 LS mean % change from baseline* –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)

10. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 10 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 Ezetimibe 10 mg + atorvastatin 10–20 mg (n=220) Placebo + atorvastatin 10–20 mg (n=230) Patients with ≥1 drug-related adverse experience 2.31.3 Gastrointestinal0.51.3 Musculoskeletal/connective tissue0.50.0 Nervous system0.90.4 Skin/subcutaneous tissue0.50.0

11. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 11 Laboratory Adverse Experiences n/N* Ezetimibe 10 mg + atorvastatin 10–20 mg (n=220) Placebo + atorvastatin 10–20 mg (n=230) Blood bilirubin increased1/2180/226 Blood potassium increased1/10** Creatine kinase increased0/2181/227 Fasting blood glucose increased0/2091/223 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 postbaseline value for the lab test

12. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 12 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 ≥3  ULN, or a measurement ≥3  ULN followed by a measurement <3  ULN taken more than three days after last dose of study medication. % Patients Parameter Ezetimibe 10 mg + atorvastatin 10–20 mg (n=220) Placebo + atorvastatin 10–20 mg (n=230)p Value ALT ≥3  ULN* 0.50.0NS AST ≥3  ULN* 0.50.0NS CK ≥3  ULN 0.0 NS

13. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 13 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

14. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 14 References Please see notes page.

15. Downloaded from www.ezetrol.aewww.ezetrol.ae Slide 15 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 product in 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-SSPrinted in USA