1. Leadership. Knowledge. Community. 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 Guidelines

2. 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.

3. 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.

4. Polling question Do you offer low dose ASA to Alex? A. Yes B. No © 2011 - TIGC

5. Primary prevention What else do you want to know? Hypertension Diabetes Lipids Risk score BMI Age Sex Family history Smoking Bleeding Risk Risk factors © 2011 - TIGC

6. 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 prevention Antithrombotic trialists’ collaboration © 2011 - TIGC

7. 6 primary prevention trials ASA vs Placebo 95 000 individuals 660 000 person- years 3554 serious vascular events Primary prevention Antithrombotic trialists’ collaboration 16 secondary prevention trials 17 000 individuals 43 000 person-years 3306 serious vascular events © 2011 - TIGC

8. Serious vascular events in ATTC primary prevention trials Lancet 2009;373:1849-60. © 2011 - TIGC

9. Relative risk reduction Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. RR Primary prevention Serious vascular events in ATTC primary © 2011 - TIGC

10. Do you offer low dose ASA to Alex? A. Yes B. No Polling question © 2011 - TIGC

11. NNT 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

12. Primary Prevention What about bleeding? Net Clinical Benefit NNH 1000 NNT 415 NCB NNT 714 NNT 47.2 NCB NNT 49.5 NNH 2500 NNT 1000 NCB NNT 1666 NNT 70 NCB NNT 73.5 Lancet 2009;373:1849-60. NNT – Number needed to treat for 1 year to prevent a single event

13. Primary prevention Demographic subgroups RRR ASA vs Placebo NNT20006257692500 Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. RR ASA vs Placebo © 2011 - TIGC

14. Is it Alex or Alexis? Primary prevention Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGC

15. Primary prevention risk reduction of serious vascular events Risk factor sub-groups RR ASA vs Placebo Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. NNT909250099991250 © 2011 - TIGC

16. RR ASA vs Placebo NNT6677146251000 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 - TIGC

17. Primary prevention risk reduction of serious vascular events 10-year risk sub-groups RR ASA vs Placebo NNT2500476416-666 Baigent C, Blackwell L, Collins R, et al. Lancet 2009;373:1849-60. © 2011 - TIGC

18. 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 © 2011 - TIGC

19. PRIMARY PREVENTION IN HIGH-RISK PATIENTS

20. 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

21. Dual antiplatelet therapy in primary prevention © 2011 - TIGC

22. n=3284 n=12,153 n=15,603 CHARISMA Treatment effect by inclusion criteria Combined end point: MI, stroke, CV death 0.51.01.5 Placebo better Clopidogrel better Risk Factor Only Manifest All patients Hazard ratioRR (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

23. 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. 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. 25 ® Primary prevention of vascular events

26. 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

27. 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

28. “What if” Alex has: Bilateral carotid bruits? Reduced Ankle Brachial Index? Severe chronic kidney disease? © 2011 - TIGC

29. “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. 30 ® Primary Prevention of Vascular Events

31. © 2011 - TIGC