Therapy for the Primary Prevention of Vascular Events Working Group Alan D Bell MD CCFP and James D Douketis MD FRCP Canadian Cardiovascular Society Antiplatelet Guidelines Objectives ID: 372607
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Antiplatelet Therapy for the Primary Prevention of Vascular Events
Working Group: Alan D. Bell, MD, CCFP and James D. Douketis, MD, FRCP
Canadian Cardiovascular Society Antiplatelet GuidelinesSlide2
Objectives© 2011 - TIGCInterpret 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.Slide3
Alex© 2011 - TIGCAlex 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.Slide4
Polling questionDo you offer low dose ASA to Alex?
Yes No© 2011 - TIGCSlide5
Primary preventionWhat else do you want to know?
Hypertension Diabetes Lipids Risk score BMIAge Sex Family history Smoking Bleeding Risk
Risk factors
© 2011 - TIGCSlide6
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 - TIGCSlide7
6 primary prevention trialsASA vs Placebo95 000 individuals660 000 person- years
3554 serious vascular eventsPrimary preventionAntithrombotic trialists’ collaboration16 secondary prevention trials17 000 individuals43 000 person-years3306 serious vascular events
© 2011 - TIGCSlide8
Serious vascular events in ATTC primary prevention trials
Lancet 2009;373:1849-60.
© 2011 - TIGCSlide9
Relative risk reduction
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. RRPrimary preventionSerious vascular events in ATTC primary
© 2011 - TIGCSlide10
Do you offer low dose ASA to Alex? Yes
NoPolling question© 2011 - TIGCSlide11
NNT
Absolute risk reductionPrimary PreventionBaigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. Serious
vascular events in ATTC primary
1428
67
© 2011 - TIGCSlide12
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 eventSlide13
Primary prevention Demographic subgroups
RRR ASA vs PlaceboNNT20006257692500
Baigent
C, Blackwell L, Collins R, et al
.
Lancet 2009;373:1849-60.
RR ASA
vs
Placebo
© 2011 - TIGCSlide14
Is it Alex or Alexis?Primary prevention
Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGCSlide15
Primary prevention risk reduction of serious vascular eventsRisk factor sub-groups
RR ASA vs PlaceboBaigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60.
NNT
909
2500
9999
1250
© 2011 - TIGCSlide16
RR
ASA vs PlaceboNNT667
714
625
1000
Primary prevention risk reduction of serious vascular events
Risk factor sub-groups
Baigent C, Blackwell L, Collins R, et al
.
Lancet 2009;373:1849-60.
© 2011 - TIGCSlide17
Primary prevention risk reduction of serious vascular events 10-year risk sub-groups
RR ASA vs PlaceboNNT2500
476
416
-666
Baigent C, Blackwell L, Collins R, et al
.
Lancet 2009;373:1849-60.
© 2011 - TIGCSlide18
Lancet 2009;373:1849-60.
“It did not depend significantly on age, sex, smoking history, blood pressure, total cholesterol, body-mass index, history of diabetes, or predicted risk of coronary heart disease.”
Risk Factors and the Benefit of ASA in Primary Prevention
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© 2011 - TIGCPRIMARY PREVENTION IN HIGH-RISK PATIENTSSlide20
Ongoing trialsARRIVE (Aspirin to Reduce Risk of Initial Vascular Events)12,000 patients20-30% 10-year risk of an event associated with
CVD or 10-20% 10-year risk of an event associated with Coronary Heart Disease (CHD).ASPREE19,000 patientsAge > 70 years© 2011 - TIGCSlide21
Dual antiplatelet therapy in primary prevention
© 2011 - TIGCSlide22
n=3284n=12,153
n=15,603CHARISMA Treatment effect by inclusion criteriaCombined end point: MI, stroke, CV death
0.5
1.0
1.5
Placebo
better
Clopidogrel
better
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
© 2011 - TIGCSlide23
Antiplatelet Therapy for the Primary Prevention of Vascular EventsRECOMMENDATIONS
Working Group: Alan D. Bell, MD, CCFP and James D. Douketis, MD, FRCPSlide24
Antiplatelet Therapy for the Primary Prevention of Vascular EventsFor 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).
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).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).Slide25
Primary prevention of vascular eventsSlide26
AlexAlex 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 - TIGCSlide27
AlexLifestyle interventions are recommended to reduce his CV risk including:
Regular exerciseLow-fat, low-salt dietSmoking cessation (if appropriate)BP and lipid monitoringLow dose ASA is not recommended© 2011 - TIGCSlide28
“What if”Alex has:Bilateral carotid bruits?Reduced Ankle Brachial Index?
Severe chronic kidney disease?© 2011 - TIGCSlide29
“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.© 2011 - TIGCSlide30
Primary Prevention of Vascular EventsSlide31
© 2011 - TIGC