leadership. knowledge. community. antiplatelet therapy for the primary prevention of vascular events...
TRANSCRIPT
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Leadership. Knowledge. Community.
Antiplatelet Therapy for the Primary Prevention of Vascular EventsWorking Group: Alan D. Bell, MD, CCFP and James D. Douketis, MD, FRCP
Canadian Cardiovascular Society Antiplatelet Guidelines
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Objectives
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Interpret the Canadian Cardiovascular Society Guideline recommendations regarding the use of antiplatelet therapy for primary prevention of vascular events.
Distinguish the clinical impact of absolute versus relative risk reduction in primary prevention.
Distinguish the effect of risk factors on the clinical impact of antiplatelet therapy for primary prevention.
Evaluate the evidence supporting the recommendations regarding the use of antiplatelet therapy in primary prevention.
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Alex
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Alex is accompanying his wife who is seeing you in follow up for her coronary disease. Alex wants to know if he should be taking ASA to prevent a heart attack.
Alex is 65 and has never had any manifestation of vascular disease.
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Polling question
Do you offer low dose ASA to Alex?
A. YesB. No
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Primary preventionWhat else do you want to know?
Hypertension Diabetes Lipids Risk score BMI
Age Sex Family history Smoking Bleeding Risk
Risk factors
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Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.
Lancet 2009; 373: 1849–60
Primary preventionAntithrombotic trialists’ collaboration
© 2011 - TIGC
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6 primary prevention trials
ASA vs Placebo
95 000 individuals
660 000 person- years
3554 serious vascular events
Primary preventionAntithrombotic trialists’ collaboration
16 secondary prevention trials
17 000 individuals
43 000 person-years
3306 serious vascular events
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Serious vascular events in ATTC primary prevention trials
Lancet 2009;373:1849-60. © 2011 - TIGC
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Maj Cor Event Non Fat MI Maj Vasc Event0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
PrimarySecondary
Relative risk reduction
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60.
RRPrimary preventionSerious vascular events in ATTC primary
© 2011 - TIGC
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Do you offer low dose ASA to Alex?A. Yes
B. No
Polling question
© 2011 - TIGC
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Maj Cor Event Non Fat MI Maj Vasc Event0
200400600800
100012001400160018002000
PrimarySecondary
NN
T
Absolute risk reduction
Primary Prevention
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60.
Serious vascular events in ATTC primary
1428
67
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Primary Prevention What about bleeding? Net Clinical Benefit
NNH 1000
NNT 415
NCBNNT 714
NNT 47.2
NCBNNT 49.5
NNH 2500
NNT 1000
NCBNNT 1666
NNT 70
NCBNNT73.5
Lancet 2009;373:1849-60. NNT – Number needed to treat for 1 year to prevent a single event
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Primary prevention Demographic subgroups
Age Sex0
0.10.20.30.40.50.60.70.80.9
1
< 65 / M>65 / F
RRR
ASA
vs P
lace
bo
NNT 2000 625 769 2500
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60.
RR A
SA v
s Pl
aceb
o
© 2011 - TIGC
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Is it Alex or Alexis?Primary prevention
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGC
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Primary prevention risk reduction of serious vascular eventsRisk factor sub-groups
HTN Smoking0
0.10.20.30.40.50.60.70.80.9
1
YesNo
RR A
SA v
s Pl
aceb
o
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60.
NNT 909 2500 9999 1250
© 2011 - TIGC
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sBP > 160 dBP > 90 TC > 6.0 BMI > 300
0.10.20.30.40.50.60.70.80.9
1
RR A
SA v
s Pl
aceb
o
NNT 667 714 625 1000
Primary prevention risk reduction of serious vascular eventsRisk factor sub-groups
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGC
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Primary prevention risk reduction of serious vascular events 10-year risk sub-groups
< 5% 5-10 % 10-20% >20%0
0.2
0.4
0.6
0.8
1
1.2
RR A
SA v
s Pl
aceb
o
NNT 2500 476 416 -666
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGC
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PRIMARY PREVENTION IN HIGH-RISK PATIENTS
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Ongoing trials
ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)
12,000 patients
20-30% 10-year risk of an event associated with CVD or 10-20% 10-year risk of an event associated with Coronary Heart Disease (CHD).
ASPREE
19,000 patients
Age > 70 years
© 2011 - TIGC
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Dual antiplatelet therapy in primary prevention
© 2011 - TIGC
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n=3284
n=12,153
n=15,603
CHARISMA Treatment effect by inclusion criteria
Combined end point: MI, stroke, CV death
0.5 1.0 1.5Placebobetter
Clopidogrelbetter
Risk Factor Only
Manifest
All patients
Hazard ratio RR (95% CI)
1.20 (0.91–1.59)
0.88 (0.77–0.998)
0.93 (0.83–1.05)
Bhatt DL, et al. N Engl J Med 2006;354(16):1706-1717.
p=0.20
p=0.046
p=0.22
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Leadership. Knowledge. Community.
Antiplatelet Therapy for the Primary Prevention of Vascular Events
RECOMMENDATIONS
Working Group: Alan D. Bell, MD, CCFP and James D. Douketis, MD, FRCP
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24®
Antiplatelet Therapy for the Primary Prevention of Vascular Events
1. For men and women without evidence of manifest vascular disease, the use of ASA at any dose is not recommend for routine use to prevent ischemic vascular events (Class III, Level A).
2. For men and women without evidence of manifest vascular disease, the use of clopidogrel 75 mg daily plus ASA at any dose is not recommended to prevent ischemic vascular events (Class III, Level B).
3. In special circumstances in men and women without evidence of manifest vascular disease in whom vascular risk is considered high and bleeding risk low, ASA 75-162 mg daily may be considered (Class IIb, Level C).
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25®
Primary prevention of vascular events
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Alex
Alex is accompanying his wife who is seeing you in follow up for her coronary disease. Alex wants to know if he should be taking ASA to prevent a heart attack.
Alex is 65 and has never had any manifestation of vascular disease.
© 2011 - TIGC
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Alex
Lifestyle interventions are recommended to reduce his CV risk including:
Regular exercise
Low-fat, low-salt diet
Smoking cessation (if appropriate)
BP and lipid monitoring
Low dose ASA is not recommended
© 2011 - TIGC
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“What if”
Alex has:
Bilateral carotid bruits?
Reduced Ankle Brachial Index?
Severe chronic kidney disease?
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“What if”
Although evidence is limited, ASA may be considered for primary prevention in individuals with evidence of significant asymptomatic atherosclerosis or end stage kidney disease.
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30®
Primary Prevention of Vascular Events
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