EUROPA

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(No Transcript)
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Aim

• To determine the effects of a Coversyl-based
  blood pressure lowering regimen on the risk of
  recurrent stroke among patients with a history of
  stroke or TIA.

Reference Neal B, MacMahon S. J Hypertens.
1995131869-1873.
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Study end points

• Primary outcome
• stroke (fatal or non fatal)
• Secondary outcomes
• fatal or disabling stroke
• total major vascular events (composite of
  nonfatal stroke, nonfatal myocardial infarction,
  or death due to any vascular cause)
• total and cause specific deaths
• hospital admissions
• dementia and cognitive decline

Reference Neal B, MacMahon S. J Hypertens.
1995131869-1873.
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Design
Randomization
Eligibility
Study end
Patients withhistory ofcerebrovascular disease
Coversyl arm Coversyl 4 mg diuretic
Coversyl run-in
2 mg od
4 mg od
Placebo
2 weeks
2 weeks
4 years
(open)
(double-blind)
Reference Neal B, MacMahon S. J Hypertens.
1995131869-1873.
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Baseline characteristics of randomized
participants

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Baseline characteristics of randomized
participants

SBP ? 160 mm Hg or DBP ? 90 mm Hg

Reference Lancet . 20013581033-1041.
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Blood pressure differences All participants
160
Systolic
Placebo
140
Coversyl arm
Mean blood pressure difference 9.0/4.0 mm Hg
120
Blood pressure (mm Hg)
100
Placebo
80
Coversyl arm
Diastolic
60
B
R
1
3
6
9
12
18
24
30
36
42
48
Months of follow-up


Reference Lancet . 20013581033-1041.
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Coversyl-based regimenreduces stroke
0.20
Placebo
0.15
Proportion with event
Coversyl arm
0.10
0.05
0.00
0
1
2
3
4
Follow-up time (y)
Reference Lancet 20013581033-1041.
9
Coversyl-based regimenreduces stroke
Reference Lancet . 20013581033-1041.
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Coversyl-based regimen reduces major vascular
events
0.25
26 risk reduction (95 CI 16-33) Plt0.0001
Placebo
0.20
Coversyl arm
0.15
Proportion with event
0.10
0.05
1
2
3
4
Follow-up time (y)
11
Coversyl-based regimen reduces major vascular
events
Events Coversyl arm Placebo n3051
n3054
Risk reduction (95CI)
Favors Coversyl arm
Favors placebo
Major vascular events
9 (-12 to 25) 38 (14 to 55) 29 (17 to 39) 26
(16 to 34)

• Vascular death
• Nonfatal MI
• Nonfatal stroke
• Total events

Reference Lancet .20013581033-1041.
12
Coversyl-based regimen reduces major coronary
events
0.06
26 risk reduction (95CI 6-42) P value 0.016
0.05
Placebo
0.04
Coversyl arm
Proportion with event
0.03
0.02
0.01
1
2
3
4
Follow-up time (y)
13
Coversyl-based regimen reduces total coronary
events
Placebo
0.10
21 risk reduction (95CI 6-33) P value 0.008
Coversyl arm
Proportion with event
0.05
0.00
0
1
2
3
4
Follow-up time (y)
14
Coversyl-based regimen reduces total coronary
events
Events Coversyl arm placebo
Favors Coversyl arm
Favors placebo
Risk Reduction (95CI)
60 58 63 111 233
38 (12 to 55) 7 (-34 to 35) 23 (-7 to
45) 17 (-6 to 36) 21 (6 to 33)
Outcome Nonfatal MI Death due to CHD Coronary
revascularization Unstable angina Total
coronary events
96 62 82 134 291
0.4
15
Coversyl-based regimen reduces heart failure
(Death, hospitalization or discontinuation)
0.06
26 risk reduction (95CI 5-42) P value 0.01
Placebo
0.05
Coversyl arm
0.04
Proportion with event
0.03
0.02
0.01
0.00
0
1
2
3
4
Follow-up time (y)
16
Coversyl-based regimen reduces congestive heart
failure
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Coversyl-based regimen efficacy

• 33 reduction in the risk of fatal or disabling
  stroke
• 25 reduction in the risk of less severe strokes
• 50 reduction in the risk of hemorrhagic stroke
• 25 reduction in the risk of cerebral ischemia

Reference Lancet . 20013581033-1041
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Coversyl-based regimen efficacy

• 25 reduction in the risk of major cardiovascular
  events
• 22 reduction in the risk of major coronary
  events
• 33 reduction in myocardial infarction
• All benefits achieved against a background of
  standard care that included antiplatelet and
  antihypertensive therapy

Reference Lancet . 20013581033-1041.
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Recommendations for initiation

• Acute stroke
• initiate treatment with Coversyl 4 mg once daily
  at the time of discharge or post-discharge follow
  up
• Past history of stroke or TIA
• primary care physician to initiate Coversyl 4 mg
  once daily treatment at the patients next visit

Reference Lancet . 20013581033-1041.