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

Objectives

© 2011 - TIGC

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.

Alex

© 2011 - TIGC

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.

Polling question

Do you offer low dose ASA to Alex?

A. YesB. No

© 2011 - TIGC

Primary preventionWhat else do you want to know?

Hypertension Diabetes Lipids Risk score BMI

Age Sex Family history Smoking Bleeding Risk

Risk factors

© 2011 - TIGC

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

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

© 2011 - TIGC

Serious vascular events in ATTC primary prevention trials

Lancet 2009;373:1849-60. © 2011 - TIGC

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

Do you offer low dose ASA to Alex?A. Yes

B. No

Polling question

© 2011 - TIGC

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

© 2011 - TIGC

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

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

Is it Alex or Alexis?Primary prevention

Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGC

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

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

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

© 2011 - TIGC

PRIMARY PREVENTION IN HIGH-RISK PATIENTS

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

Dual antiplatelet therapy in primary prevention

© 2011 - TIGC

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

© 2011 - TIGC

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

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).

25®

Primary prevention of vascular events

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

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

“What if”

Alex has:

Bilateral carotid bruits?

Reduced Ankle Brachial Index?

Severe chronic kidney disease?

© 2011 - TIGC

“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 - TIGC

30®

Primary Prevention of Vascular Events

© 2011 - TIGC