Transcript Slide 1

Canadian Cardiovascular Society
Antiplatelet Guidelines
Antiplatelet Therapy for Vascular
Prevention in Patients with
Peripheral Arterial Disease
Working Group: A. Roussin, MD, FRCP; Thomas F. Lindsay, MD, CM, FRCSC
Leadership. Knowledge. Community.
Objectives
Interpret the Canadian Cardiovascular Society Guideline
recommendations regarding the use of antiplatelet
therapy in patients with peripheral arterial disease.
Appropriately use antiplatelet agents in patients with
symptomatic versus asymptomatic PAD.
Appropriately use antiplatelet agents in patients following
peripheral vascular surgery.
© 2011 - TIGC
Case
A 50-year old male patient, treated for dyslipidemia
and hypertension with both a statin and a ACEI,
reports new onset of leg pain when walking.
He has recently quit smoking. There are no symptoms
suggestive of CAD or CVD.
The physical examination is unremarquable except
for a left femoral bruit and diminished tibial
pulsations on the same side.
© 2011 - TIGC
Antiplatelet management
What antiplatelet therapy, if any, would you suggest ?
A. No antiplatelet therapy
B.
ASA 80 mg
C.
Clopidogrel 75 mg
D. ASA 80 mg + Clopidogrel 75 mg
© 2011 - TIGC
Asymptomatic “PAD”
ASA ineffective (but ABI 0.86…)
CAD event with or without mortality, stroke or revascularization
Fowkes et al. JAMA 2010
© 2011 - TIGC
Asymptomatic “PAD” and Diabetes
ASA ineffective (but ABI 0.9…)
POPADAD Belch J et al. BMJ 2008
© 2011 - TIGC
% Stroke, MI and vascular death
Antiplatelet therapy impact
APT coll. Study BMJ 2002; 324: 71-86
.Antiplatelet
Control
25
22% RRR
20
25% RRR
25% RRR
15 26% RRR
10
30% RRR
11% RRR
5
0
PAD +
others
Previous
TIA or
Stroke
Acute
Stroke
Adapted
BMJ 94
Clopidogrel : CAPRIE Study
RRR according to entry criteria
ARR / yr
8.7
All patients
5.83  5.32
7.3
Stroke
7.71  7.15
- 3.7
MI
4.84  5.03
23.8
Claudication
4.86  3.71
22.7
Claudication or Stroke with
previous MI
- 40
- 30
- 20
- 10
ASA better
0
10
20
10.74  8.35
30
40
Clopidogrel better
Relative risk reduction (%)
CAPRIE. Lancet 1996; 348:pp. 1 329 à 1 339.
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®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
1. For patients with asymptomatic PAD with an ABI <0.9, lowdose ASA (75-162 mg daily) may be considered for those at
high risk because of associated atherosclerotic risk factors in
the absence of risk factors for bleeding (Class IIb, Level C).
2. For patients with symptomatic PAD without overt CAD or
cerebrovascular disease, low-dose ASA (75-162 mg daily) or
clopidogrel 75 mg daily is recommended providing the risk for
bleeding is low (Class IIb, Level B). The choice of drug may
depend on patient preference and cost considerations.
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Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
3. For patients allergic or intolerant to ASA, use of clopidogrel
is suggested (Class IIa, Level B).
4. For patients with intermittent claudication, dipyridamole
should not be used in addition to ASA (Class III, Level C).
Overall Population: Primary efficacy outcome
(MI, stroke, or CV death)†
Placebo + ASA*
7.3%
Clopidogrel +
ASA*
6.8%
Cumulative event rate (%)
8
6
4
RRR: 7.1% [95% CI: -4.5%, 17.5%]
2
p=0.22
0
0
6
12
18
24
30
Months since randomization
† First
Occurrence of MI (fatal or non-fatal), stroke (fatal or nonfatal), or cardiovascular death
*All patients received ASA 75-162mg/day
Median follow-up was 28 months
Bhatt D et al. NEJM 2006
Primary efficacy end point (MI, Stroke and CV death)
CHARISMA (CH) vs CAPRIE (CP)
28 months
ASA
28 months
ASA +
Clop.
RRR
7.3%
6.8%
7%
0.22
3.12%
AT
7.9%
6.9%
13%
0.046
RF
5.5%
6.6%
-20%
0.2
CH: ALL
CP: ALL
P value 12 months 12 months
ASA
ASA +
Clop.
ARR
Per
year
Events
saved/
1000pts/yr
ASA +
Clop.
NNT
Per yr
If p <
0.05
2.91%
0.21%
2.1
476
3.39%
2.96%
0.43%
4.3
233
2.36%
2.83%
-0.88%
-4.8
5.83%
MI/PAD
4.8%
PAD/Str.
Prev. MI
10.7%
200
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13
®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
5. For patients with intermittent claudication, using clopidogrel
75 mg daily in addition to ASA 75-162 mg daily is not
recommended unless the patient is judged to be at high
vascular risk along with a low risk of bleeding (Class IIb,
Level B).
Warfarin Antiplatelet Vascular Evaluation
Study Design - 2161 PAD Patients
Central randomization, 80 centres, 7 countries, open trial, blinded adjudication
PAD Patients
AP only
(1,081 patients)
Run-In
2-4 weeks
Rand
Follow-up - q 3 mo. x 30-42 mo.
AP + OAC
(INR 1.8-3.5)
AP + OAC
(1,080 patients)
Anand S et al. TIGC oct 2006
Co-Primary end-point 1
CV death, MI, stroke
WAVE: CVD/MI/Strk
0.10
AP
0.05
W/A
Anti
0.0
Kaplan-Meier Rates
0.15
OAC+AP
0
100
300
Anand S et al. TIGC oct 2006
500
700
Day
900
1100
1300
Co-Primary end-point 2
CV death, MI, stroke, severe ischemia
0.20
WAVE: CVD/MI/Strk/si
AP
Anti
0.10
W/A
0.0
0.05
Kaplan-Meier Rates
0.15
OAC+AP
0 100
300
Anand S et al. TIGC oct 2006
500
700
Day
900
1100
1300
Life-threatening bleeding
OAC+AP
0.04
AP
0.03
P<0.001
0.02
W/A
0.01
Kaplan-Meier Rates
0.05
WAVE: Life-threatening
0.0
Anti
0
100
300
Anand S et al. TIGC oct 2006
500
700
Day
900
1100
1300
WAVE: Outcomes in PAD patients
End point
Warfarin + ASA,
n=1080 (%)
Aspirin only,
n=1081 (%)
Hazard ratio
p
First primary
end point*
12.2
13.3
0.92
0.49
Second primary
end point†
15.9
17.4
0.91
0.38
Life-threatening
bleeding
4
1.2
3.41
<0.001
Moderate bleeding
2.9
1.0
2.82
0.0018
*CV death, MI, and stroke
†CV death, MI, stroke, and severe ischemia in the coronary or peripheral arteries
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Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
7. For patients with symptomatic PAD without compelling
indications for oral anticoagulation such as atrial fibrillation
or venous thromboembolism, oral anticoagulation should
not be added to antiplatelet therapy (Class III, Level B).
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Back to our case
A 50 year old male patient, treated for dyslipidemia
and hypertension with both a statin and a ACEI, reports
new onset of leg pain when walking.
He has recently quit smoking. There are no symptoms
suggestive of CAD or CVD.
The physical examination is unremarquable except for
a left femoral bruit and diminished tibial pulsations on
same side.
© 2011 - TIGC
Antiplatelet management
What antiplatelet therapy, if any, would you suggest ?
A.
No antiplatelet therapy
B.
ASA 80 mg
C.
Clopidogrel 75 mg
D.
ASA 80 mg + Clopidogrel 75 mg
© 2011 - TIGC
“What if”
Peripheral angioplasty
Same patient comes back to you after having a stent
implanted in his left iliac artery.
Would that change your choice of antiplatelet therapy?
© 2011 - TIGC
24
®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
9. Long-term antiplatelet therapy with ASA 75-162 mg daily
should be given to patients who undergo lower-extremity
balloon angioplasty with or without stenting for chronic
symptomatic PAD (Class IIa, Level C). Anticoagulation with
heparin or vitamin K antagonists should be avoided in this
setting (Class III, Level B).
“What if”
Infrainguinal reconstruction
Same patient comes back to you after undergoing
a femoro-popliteal bypass.
Would that change your choice of antiplatelet therapy?
© 2011 - TIGC
26
®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
10. For all infrainguinal reconstructions, low-dose ASA (75162 mg daily) should be given (Class IIa, Level B). In
those with infrainguinal grafts and a high risk of
thrombosis or limb loss, combination therapy with
a vitamin K antagonist and ASA may be of benefit
(Class IIb, Level C).
“What if”
AAA
Same patient comes back.
A 4 cm wide abdominal aortic aneurism is described
on a recent abdominal echo.
How would that change your choice of antiplatelet
therapy?
© 2011 - TIGC
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®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
11. Low-dose ASA (75-162 mg daily) may be considered for all
patients with an AAA, particularly those with clinical or
subclinical PAD (Class IIb, Level C).
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“What if”
Atrial fibrillation
Same patient comes back.
A recent ECG shows atrial fibrillation.
How would that change your choice of antiplatelet
therapy?
© 2011 - TIGC
31
®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
8. For patients with symptomatic PAD with an indication for
oral anticoagulation such as atrial fibrillation, venous
thromboembolism, heart failure or mechanical valves,
antiplatelet therapy should not be added to oral
anticoagulation (Class III, Level A).
“What if”
ACS
Same patient comes back
He was recently hospitalized for a ACS and underwent a
coronary angioplasty along with two stents deployed
How would that change your choice of antiplatelet
therapy?
© 2011 - TIGC
33
®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
6. For patients with symptomatic PAD with overt CAD
or cerebrovascular disease, antiplatelet therapy as indicated
for the CAD and/or cerebrovascular status I
s
recommended (Class I, Level A).
“What if”
TIA
Same patient comes back.
Reports a recent 20 minutes right brachio-facial
weakness.
How would that change your choice of antiplatelet
therapy?
© 2011 - TIGC
35
®
Antiplatelet therapy for vascular prevention
in patients with peripheral arterial disease
6. For patients with symptomatic PAD with overt CAD or
cerebrovascular disease, antiplatelet therapy as indicated
for the CAD and/or cerebrovascular status is recommended
(Class I, Level A).
© 2011 - TIGC