Aim To determine the effects of a Coversyl- based blood pressure lowering regimen on the risk of...

AimAim

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

Reference: Neal B, MacMahon S. J Hypertens. 1995;13:1869-1873.

Study end pointsStudy end points Primary outcome:Primary outcome:

stroke (fatal or non fatal)stroke (fatal or non fatal)

Secondary outcomes:Secondary outcomes: fatal or disabling strokefatal or disabling stroke total major vascular events (composite of nonfatal stroke, total major vascular events (composite of nonfatal stroke,

nonfatal myocardial infarction, or death due to any vascular nonfatal myocardial infarction, or death due to any vascular cause)cause)

total and cause specific deathstotal and cause specific deaths hospital admissionshospital admissions dementia and cognitive declinedementia and cognitive decline


DesignDesign

Eligibility Randomization Study end

Coversyl run-in

2 mg od 4 mg od

2 weeks 2 weeks 4 years

Placebo

Coversyl arm: Coversyl 4 mg ± diuretic

(open) (double-blind)

Patients withhistory ofcerebrovascular disease


Baseline characteristics of randomized participantsBaseline characteristics of randomized participants Randomized

treatment Characteristic Coversyl arm Placebo

Demographic n=3051 n=3054

Age, years (SD) 64 (10) 64 (10)

Female (%) 30 30

Asian (%) 39 39

Cerebrovascular disease history

Stroke (%)

Ischemic stroke 71 71

Cerebral hemorrhage 11 11

Unknown stroke 4 5

TIA or amaurosis fugax (%) 22 22

Reference: Lancet. 2001;358:1033-1041.

†SBP 160 mm Hg or DBP 90 mm HgReference: Lancet . 2001;358:1033-1041.

Randomized Treatment

Characteristic Coversyl arm Placebo

Other medical history (%)

Current smoker 20 20

Diabetes 13 12

Coronary heart disease 16 16

Blood pressure and hypertension status

Mean systolic blood pressure, mm Hg (SD) 147 (19) 147 (19)

M ean diastolic blood pressure, mm Hg (SD) 86 (11) 86 (11)

Hypertension (%) † 48 48

Antihypertensive therapy (%) 50 51

Baseline characteristics of randomized participantsBaseline characteristics of randomized participants

Blood pressure differences All participants

Blood pressure differences All participants

60

80

100

120

140

160

B R 1 3 6 9 12 18 24 30 36 42 48

Months of follow-up

Blo

od p

ress

ure

(mm

Hg)

Mean blood pressure difference 9.0/4.0 mm Hg

Coversyl arm

PlaceboSystolic

Diastolic

Reference: Lancet . 2001;358:1033-1041.

Placebo

Coversyl arm

Coversyl-based regimenreduces strokeCoversyl-based regimenreduces stroke

Follow-up time (y)

Pro

po

rtio

n w

ith

eve

nt

0 1 2 3 4

95% CI 17 - 38%

P<0.0001

28% risk reduction

0.00

0.05

0.10

0.15

0.20

Placebo

Coversyl arm

Reference: Lancet 2001;358:1033-1041.

Fatal or disabling

Nonfatal or disabling

Ischemic stroke

Cerebral hemorrhage

Stroke type unknown

Total stroke

Events Coversyl arm Placebo

n=3051 n=3054

FavorsCoversyl arm

Favorsplacebo

Risk reduction(95%CI)

33% (15 to 46)

24% (9 to 37)

24% (10 to 35)

50% (26 to 67)

18% (-24 to 45)

28% (17 to 38)

Stroke subtypes

123

201

246

37

42

307

181

262

319

74

51

420

0.5 2.0 Hazard ratio

1.0


Coversyl-based regimenreduces strokeCoversyl-based regimenreduces stroke

Follow-up time (y)

Pro

port

ion

with

eve

nt

0.05

0.10

0.15

0.20

0.25

1 2 3 4

26% risk reduction(95% CI 16-33%)

P<0.0001

Coversyl-based regimen reduces major vascular eventsCoversyl-based regimen reduces major vascular events

Placebo

Coversyl arm

Vascular death

Nonfatal MI

Nonfatal stroke

Total events

Risk reduction(95%CI)

9% (-12 to 25)

38% (14 to 55)

29% (17 to 39)

26% (16 to 34)

Major vascular events

FavorsCoversyl arm

Favorsplacebo

181

60

275

458

198

96

380

604

Events Coversyl arm Placebo

n=3051 n=3054

0.5 2.0

Hazard ratio

1.0

Coversyl-based regimen reduces major vascular eventsCoversyl-based regimen reduces major vascular events

Reference: Lancet .2001;358:1033-1041.

26% risk reduction(95%CI 6-42%)P value = 0.016

Follow-up time (y)

Pro

po

rtio

n w

ith

eve

nt

0.01

0.02

0.03

0.04

0.05

0.06

1 2 3 4

Coversyl-based regimen reduces major coronary eventsCoversyl-based regimen reduces major coronary events

Placebo

Coversyl arm

0.00

0.05

0.10

0 1 2 3 4


Follow-up time (y)

Pro

port

ion

with

eve

nt

Coversyl-based regimen reduces total coronary eventsCoversyl-based regimen reduces total coronary events

Placebo

Coversyl arm

0.4

Outcome

Nonfatal MI

Death due to CHD

Coronary revascularization

Unstable angina Total coronary events

Events Coversyl arm placebo

FavorsCoversyl arm

Favorsplacebo

60

58

63

111

233

96

62

82

134

291

38% (12 to 55%)

7% (-34 to 35%)

23% (-7 to 45%)

17% (-6 to 36%)

21% (6 to 33%)

Risk Reduction(95%CI)

Odds ratio

1.0 2.0

Coversyl-based regimen reduces total coronary eventsCoversyl-based regimen reduces total coronary events

Coversyl-based regimen reduces heart failure (Death, hospitalization or discontinuation)

Coversyl-based regimen reduces heart failure (Death, hospitalization or discontinuation)

0.00

0.01

0.02

0.03

0.04

0.05

0.06

0 1 2 3 4


Follow-up time (y)

Pro

port

ion

with

eve

nt

Coversyl arm

Placebo

Coversyl-based regimen reduces congestive heart failureCoversyl-based regimen reduces congestive heart failure

Effects in all participants

Total CHF

Effects in subgroups

Combination therapy

Single drug therapy

Hypertensive

Not hypertensive

CHD at baseline

No CHD at baseline

Events Coversyl arm placebo

FavorsCoversyl arm

Favorsplacebo

113

58

55

56

57

37

76

151

69

82

75

76

59

92

26% (5 to 42%)

34% (7 to 53%)

16% (-19 to 31%)

27% (-3 to 48%)

27% (-4 to 49%)

41% (10 to 61%)

18% (-11 to 40%)

Odds ratio

Risk Reduction(95%CI)

0.4 1.0 2.0

33% reduction in the risk of fatal or disabling 33% reduction in the risk of fatal or disabling strokestroke

25% reduction in the risk of less severe strokes25% reduction in the risk of less severe strokes

50% reduction in the risk of hemorrhagic stroke50% reduction in the risk of hemorrhagic stroke

25% reduction in the risk of cerebral ischemia25% reduction in the risk of cerebral ischemia

Reference: Lancet . 2001;358:1033-1041

Coversyl-based regimen efficacyCoversyl-based regimen efficacy

25% reduction in the risk of major cardiovascular 25% reduction in the risk of major cardiovascular eventsevents

22% reduction in the risk of major coronary events22% reduction in the risk of major coronary events 33% reduction in myocardial infarction33% reduction in myocardial infarction All benefits achieved against a background of All benefits achieved against a background of

standard care that included antiplatelet and standard care that included antiplatelet and antihypertensive therapy antihypertensive therapy


Coversyl-based regimen efficacyCoversyl-based regimen efficacy

Recommendations for initiationRecommendations for initiation

Acute strokeAcute stroke initiate treatment with Coversyl 4 mg once daily at initiate treatment with Coversyl 4 mg once daily at

the time of discharge or post-discharge follow upthe time of discharge or post-discharge follow up

Past history of stroke or TIAPast history of stroke or TIA primary care physician to initiate Coversyl 4 mg primary care physician to initiate Coversyl 4 mg

once daily treatment at the patient’s next visitonce daily treatment at the patient’s next visit


Aim To determine the effects of a Coversyl- based blood pressure lowering regimen on the risk of...

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