1. Slide 1 Downloaded from www.cozaar.aewww.cozaar.ae Population Impact of Losartan Use on Stroke in the European Union (EU)

2. Slide 2 Downloaded from www.cozaar.aewww.cozaar.ae Reprinted by permission from the Journal of Human Hypertension/Macmillan Publishers Ltd.

3. Downloaded from www.cozaar.aewww.cozaar.ae Slide 3 A Landmark Study Investigator-initiated, prospective, double-blind, active- controlled, intention-to-treat, community-based study comparing the effect of losartan vs. atenolol in reducing CV morbidity and mortality in hypertensive patients with LVH  9193 patients, 55–80 years of age  Mean 4.8-year follow-up  44,119 patient-years of follow-up  945 study sites in 7 countries  1096 patients with primary endpoints CV=cardiovascular; LVH=left ventricular hypertrophy Adapted from Dahlöf B et al Lancet 2002;359:995–1003. Ref 2, p 995, C2, ¶4, L14-20; p 996, C1, ¶2, L1-3; p 998, C2, ¶1, ¶2, L2

4. Downloaded from www.cozaar.aewww.cozaar.ae Slide 4  Age 55–80 years  Previously treated or untreated hypertension  Diastolic BP 95–115 mmHg or systolic BP 160–200 mmHg  ECG-confirmed LVH –Cornell Voltage Product >2440 mm  msec –Sokolow-Lyon >38 mm Inclusion Criteria ECG=electrocardiography Adapted from Dahlöf B et al Am J Hypertens 1997;10:705–713. Ref 1, p 708, C2, ¶1, L1-8, ¶2, L8-11

5. Downloaded from www.cozaar.aewww.cozaar.ae Slide 5 0 2 4 6 8 10 12 14 16 Proportion of patients with first event (%) Primary composite of CV death, stroke, and MI* Losartan Atenolol Benefits Beyond Blood Pressure Control: Primary Composite Endpoint and Stroke Adjusted risk reduction 13.0%, p=0.021 Unadjusted risk reduction 14.6%, p=0.009 *No significant differences in CV death and MI vs. atenolol Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Study month 0612182430364248546066 Losartan (n)46054524446043924312424741894112404738971889901 Atenolol (n)45884494441443494289420541354066399238211854876 Number at risk Losartan Atenolol Adjusted risk reduction 24.9%, p=0.001 Unadjusted risk reduction 25.8%, p=0.0006 0612182430364248546066 0 1 2 3 4 5 6 7 8 Losartan 4605 4528 4469 4408 4332 4273 4224 4166 4117 3974 1928 925 Atenolol 4588 4490 4424 4372 4317 4245 4180 4119 4055 3894 1901 897 Fatal and nonfatal stroke Proportion of patients with first event (%) Ref 1, p 999, Fig 4, Fig 5, middle Study month

6. Downloaded from www.cozaar.aewww.cozaar.ae Slide 6 EU Stroke Impact Study: Objectives  To estimate the number of strokes that could be averted in the EU with the use of losartan-based therapy in comparison to atenolol-based therapy in patients with hypertension and LVH confirmed by ECG  To project the reduction in stroke observed with a losartan- vs. an atenolol-based antihypertensive treatment regimen in the LIFE study to the EU population Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Ref 1, p 2, C1, ¶3,4

7. Downloaded from www.cozaar.aewww.cozaar.ae Slide 7 EU Stroke Impact Study: Methods  Projection was based on a combination of the following estimates –Number of individuals meeting LIFE criteria National census figures Population-based hypertension prevalence ECG-LVH prevalence from LIFE pilot study CHF prevalence (exclusion criteria) from NHANES III –Cumulative incidence of stroke from LIFE database  Projection subject to one-way sensitivity analysis Ref 1, p 2, C2, ¶2, L1-4 p 2, C1, ¶4 p 2, C2, ¶3 p 3, C1, ¶3 p 3, C1, ¶4, L4-7 p 3, C2, ¶2, L1-2 p 3, ¶3, L1-2 Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004.

8. Downloaded from www.cozaar.aewww.cozaar.ae Slide 8 Results: Estimated EU Population Meeting the LIFE Entry Criteria 377.4 million residents in EU in 2000 90.3 million were aged 55–80 years 45.7 million had hypertension 10.1 million met LVH criteria (exclude those with heart failure) 7.8 million met main LIFE inclusion criteria Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Ref 1, p 4, C1, ¶1

9. Downloaded from www.cozaar.aewww.cozaar.ae Slide 9 Example Calculation  LIFE criteria population x LIFE difference in stroke risk reduction = projected number of strokes averted  Germany: 2,214,900 (2.7 % of total population meet LIFE criteria) x difference in cumulative incidence of stroke from LIFE (atenolol vs. losartan at 5.5 years): 1.6% (CI 0.6, 2.6) = 35,438 strokes averted Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Ref 1, p 4, C1, ¶2, L9, Table 1 (Germany); p 4, C2, L2,3, Table 2, last L

10. Downloaded from www.cozaar.aewww.cozaar.ae Slide 10 Projected First Strokes Averted with Losartan vs. Atenolol in the EU After 5.5 Years of Treatment Strokes averted 1.Austria 2.Belgium 3.Denmark 4.Finland 5.France 6.Germany 7.Greece 8.Ireland 9.Italy 10.Luxembourg 11.Portugal 12.Spain 13.Sweden 14.The Netherlands 15.United Kingdom 3117 2312 1498 1576 18,430 35,438 3448 870 19,170 88 3196 12,877 2725 3050 17,472 EU total 125,267 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Ref 1, p 5, Table 3 Note: Among 7.8 million who would qualify for the LIFE trial Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004.

11. Downloaded from www.cozaar.aewww.cozaar.ae Slide 11 Projected Cumulative Number of First Stroke Events Potentially Averted with Losartan- vs. Atenolol-Based Regimen in the EU over 5.5 Years Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. No. of strokes averted 0 130,000 0 120,000 110,000 100,000 90,000 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10,000 12345 Year Ref 1, p 5, Fig 2

12. Downloaded from www.cozaar.aewww.cozaar.ae Slide 12 One-Way Sensitivity Analysis: Impact of Losartan- vs. Atenolol-Based Therapy to Potentially Avert Strokes in EU: High, Low Estimates 46,976 203,562 84,728 148,663 143,121 107,417 51,246 227,761 0 50,000 100,000 150,000 200,000 250,000 Prevalence of LVH Stroke cumulative incidence difference No. of strokes averted Low Estimate High Estimate Prevalence of hypertension Prevalence of CHF Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Ref 1, p 5, Fig 3

13. Downloaded from www.cozaar.aewww.cozaar.ae Slide 13 Conclusion: Population Impact of Losartan- Based Therapy to Avoid Strokes in the EU  7.8 million meet LIFE criteria in the EU, representing 2.1% of the total EU population  If losartan-based therapy was implemented for these patients instead of conventional beta-blocker therapy, an estimated 125,267 additional first strokes could be avoided in a 5.5-year period*  Losartan-based therapy has the potential to have a major public health impact by reducing morbidity, mortality, and costs of stroke in the EU *Based on the stroke cumulative risk difference observed in LIFE Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Ref 1, p 6,C1, ¶1, L7-13, C2, ¶2, L6-9

14. Downloaded from www.cozaar.aewww.cozaar.ae Slide 14 Bibliography Dahlöf B, Burke TA, Krobot K et al. Population impact of losartan use on stroke in the European Union (EU): Projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. J Hum Hypertens advance online publication. Available at: doi:10.1038/sj.jhh.1001710. Accessed March 18, 2004. Dahlöf B, Devereux R, de Faire U et al. The Losartan Intervention For Endpoint reduction (LIFE) in hypertension study. Rationale, design, and methods. Am J Hypertens 1997;10:705–713. Dahlöf B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002;359:995–1003.

15. Downloaded from www.cozaar.aewww.cozaar.ae Slide 15 Population Impact of Losartan Use on Stroke in the European Union (EU) Before prescribing, please consult the manufacturers’ prescribing information. Merck does not recommend the use of any product in any different manner than as described in the prescribing information. Copyright © 2004 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.CZR 2004-W-7050-SSPrinted in USA VISIT US ON THE WORLD WIDE WEB AT http://www.merck.com