Canadian Cardiovascular Society Antiplatelet Guidelines Antiplatelet Therapy for

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

Antiplatelet therapy impact APT coll. Study BMJ 2002; 324: 71 -86

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 Claudication 4. 86 3. 71 22. 7 Claudication or Stroke with previous MI - 40 - 30 4. 84 5. 03 23. 8 - 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.

® 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. 9

® 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). 10

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 0 p=0. 22 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 -162 mg/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 + 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 ASA + Clop. ARR Per year Events saved/ 1000 pts/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 42

® 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). 13

Warfarin Antiplatelet Vascular Evaluation Study Design - 2161 PAD Patients Central randomization, 80 centres, 7 countries, open trial, blinded adjudication AP only on ly PAD Patients AP (1, 081 patients) 2 -4 weeks Rand (INR 1. 8 -3. 5) + AP C OA AP + OAC Follow-up - q 3 mo. x 30 -42 mo. AP + OAC or Fin 42 al mo Vi sit. Run-In (1, 080 patients) Anand S et al. TIGC oct 2006

Co-Primary end-point 1 CV death, MI, stroke OAC+AP AP Anand S et al. TIGC oct 2006

Co-Primary end-point 2 CV death, MI, stroke, severe ischemia OAC+AP AP Anand S et al. TIGC oct 2006

Life-threatening bleeding OAC+AP AP P<0. 001 Anand S et al. TIGC oct 2006

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

® 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). 19

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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

® 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). 24

“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

® 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). 26

“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

® 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). 28

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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

® 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). 31

“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

® 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). 33

“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

® 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). 35

© 2011 - TIGC