Transcript Title slide

Population Impact
of Losartan Use on Stroke
in the European Union (EU)
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Slide 1
Reprinted by permission from the Journal of Human Hypertension/Macmillan Publishers Ltd.
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Slide 2
A Landmark Study
Investigator-initiated, prospective, double-blind, activecontrolled, intention-to-treat, community-based study
comparing the effect of losartan vs. atenolol in reducing
CV morbidity and mortality in hypertensive patients
with LVH
Ref 2, p 995,
C2, ¶4, L14-20;
p 996, C1, ¶2,
L1-3; p 998,
C2, ¶1, ¶2, L2
 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.
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Slide 3
Inclusion Criteria
 Age 55–80 years
 Previously treated or untreated hypertension
 Diastolic BP 95–115 mmHg or
Ref 1, p 708,
C2, ¶1, L1-8, ¶2,
L8-11
systolic BP 160–200 mmHg
 ECG-confirmed LVH
– Cornell Voltage Product >2440 mm  msec
– Sokolow-Lyon >38 mm
ECG=electrocardiography
Adapted from Dahlöf B et al Am J Hypertens 1997;10:705–713.
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Slide 4
Benefits Beyond Blood Pressure Control:
Primary Composite Endpoint and Stroke
Primary composite of CV death, stroke, and MI*
Atenolol
Proportion of patients
with first event (%)
14
12
10
Losartan
8
6
4
Adjusted risk reduction
13.0%, p=0.021
Unadjusted risk reduction 14.6%, p=0.009
2
Atenolol
7
6
5
Losartan
4
3
2
Adjusted risk reduction 24.9%, p=0.001
Unadjusted risk reduction 25.8%, p=0.0006
1
0
0
0
6
12
18
24
30
36
42
48
54
60
66
0
6
12
18
Study month
Number
at risk
Ref 1,
p 999,
Fig 4,
Fig 5,
middle
Fatal and nonfatal stroke
8
Proportion of patients
with first event (%)
16
24
30
36
42
48
54
60
66
Study month
Losartan (n)
4605
4524
4460
4392
4312
4247 4189
4112
4047
3897
1889
901
Atenolol (n)
4588
4494
4414
4349
4289
4205 4135
4066
3992
3821
1854
876
Losartan
Atenolol
4605
4588
4528
4490
4469 4408
4424 4372
4332
4317
4273 4224
4245 4180
4166 4117
4119 4055
3974 1928
3894 1901
925
897
*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.
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Slide 5
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
Ref 1,
p 2,
C1,
¶3,4
 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.
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Slide 6
EU Stroke Impact Study: Methods
 Projection was based on a combination of the
Ref 1,
following estimates
– Number of individuals meeting LIFE criteria
p 2, C2, ¶2, L1-4
 National census figures
p 2, C1, ¶4
 Population-based hypertension prevalence
p 2, C2, ¶3
 ECG-LVH prevalence from LIFE pilot study
p 3, C1, ¶3
 CHF prevalence (exclusion criteria) from NHANES III
p 3, C1, ¶4, L4-7
– Cumulative incidence of stroke from LIFE database
 Projection subject to one-way sensitivity analysis
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.
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Slide 7
Results: Estimated EU Population Meeting
the LIFE Entry Criteria
377.4 million residents in EU in 2000
Ref 1,
p 4, C1,
¶1
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.
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Slide 8
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
Ref 1,
p 4, C1,
¶2, L9,
Table 1
(Germany);
p 4, C2,
L2,3,
Table 2,
last L
Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710.
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Slide 9
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
EU total
3117
2312
1498
1576
18,430
35,438
3448
870
19,170
88
3196
12,877
2725
3050
17,472
13
4
Ref 1,
p 5, Table 3
3
8
15
14
2
10
6
1
5
9
11
12
125,267
7
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.
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Slide 10
No. of strokes averted
Projected Cumulative Number of First Stroke
Events Potentially Averted with Losartan- vs.
Atenolol-Based Regimen in the EU over 5.5 Years
130,000
120,000
110,000
100,000
90,000
80,000
70,000
60,000
50,000
40,000
30,000
20,000
10,000
0
Ref 1,
p 5, Fig 2
0
1
2
3
4
5
Year
Adapted from Dahlöf B et al. J Hum Hypertens. Advance online publication. Available at doi:10.1038/sj.jhh.1001710.
Accessed March 18, 2004.
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Slide 11
One-Way Sensitivity Analysis: Impact of Losartanvs. Atenolol-Based Therapy to Potentially Avert
Strokes in EU: High, Low Estimates
Low Estimate
High Estimate
250,000
No. of strokes averted
227,761
203,562
200,000
148,663
150,000
Ref 1,
p 5, Fig 3
143,121
107,417
100,000
50,000
0
84,728
51,246
Prevalence
of LVH
46,976
Stroke cumulative
incidence difference
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.
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Slide 12
Conclusion: Population Impact of LosartanBased 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
Ref 1,
p 6,C1, ¶1,
L7-13, C2,
¶2, L6-9
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.
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Slide 13
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.
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Slide 14
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-SS
Printed in USA
VISIT US ON THE WORLD WIDE WEB AT http://www.merck.com
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Slide 15