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.
Post on 03-Jan-2016
216 Views
Preview:
Transcript
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
Reference: Neal B, MacMahon S. J Hypertens. 1995;13:1869-1873.
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
Reference: Neal B, MacMahon S. J Hypertens. 1995;13:1869-1873.
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
Reference: Lancet . 2001;358:1033-1041.
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
21% risk reduction(95%CI 6-33%)P value = 0.008
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
26% risk reduction(95%CI 5-42%)P value = 0.01
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
Reference: Lancet . 2001;358:1033-1041.
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
Reference: Lancet . 2001;358:1033-1041.
top related