Aspirine pour tous les patients à haut risque?

Aspirine pour tous les patients à haut risque? Gilles Lemesle, Centre Hémodynamique, CHRU de Lille Cliquez pour modifier le style des sous titres du masque

The clinical point of view Ratio Ischaemic events Bleeding

What does High Risk mean? 1 Primary Prevention Diabetics High Risk of CAD (>20) at 10 years or High Risk of Cardiovascular Death (>5) at 10 years => Risk Scale +++ 2 Secondary Prevention

Framingham Model (Male) Step 1: Age Step 2: HDL cholestérol Step 3 : Total Cholestérol Step 4 : Systolic Blood Pressure (mmhg) Ans Points g/l Points g/l Points Non Traitée Traitée Points 30 34 0 0.6 2 < 1,6 0 <120 2 35 39 2 0,50 0,59 1 1,60 1,99 1 120 129 <120 0 40 44 5 0,45 0,49 0 2,00 2,39 2 130 139 1 45 49 6 50 54 8 55 59 10 60 64 11 0,35 0,44 1 < 0,35 2 2,40 2,79 3 280 + 4 140 159 120 129 2 160+ 130 139 3 140 159 4 65 69 12 160+ 5 70 74 14 Step 5 : Tobacco Step 6 : Diabetes Step 7 : Total 75+ 15 Points Points Points Non 0 Non 0 Oui 4 Oui 3 North American Population. Not evaluated in France. D Agostino R. B. et al., General cardiovascular risk profile for use in primary care: the framingham heart study, Circulation 2008; 117;742 753

Framingham Model (Male) Points RCV global () 18 + > 30 17 29,4 16 25,3 High Risk 20 15 21,6 14 18,4 13 15,6 12 13,2 11 11,2 10 9,4 9 7,9 8 6,7 Step 8: Estimation of the Risk at 10 years 7 5,6 6 4,7 5 3,9 4 3,3 3 2,8 2 2,3 1 1,9 0 1,6 1 1,4 2 1,1 3 < 1

SCORE Model Low risk country Belgique France Grèce Italie Luxembourg Espagne Suisse Portugal Conroy R.M., Estimation of ten year risk of fattal cardiovascular disease in europe : the SCORE project; European Heart journal (2003) 24, 987 1003 For low risk population

What dose of aspirin? Primary Prevention: What about Diabetics?

The Pro Aspirin Evidence: Primary Prevention Antithrombotic Trialist Collaboration Antithrombotic Trialist Collaboration. BMJ 2002;324:71

The Cons The POPADAD: Primary endpoint Death and/or stroke n=1276 Copyright 2008 BMJ Publishing Group Ltd. Belch, J. et al. BMJ 2008;337:a1840

Secondary endpoints

The Pro and Cons JPAD: Primary End Point: Total Atherosclerotic Events According to the Treatment Groups 1 0 8 6 Log Rank Test, P = 0.16 HR (95 CI): 0.80 (0.58 1.10) 4 2 Aspirin Group Nonaspirin Group Nonaspirin Group (n) Aspirin Group ( ) 0 0 12 1 12 2 11 3 11 4 8 5 1 Year s 77 12 20 12 65 11 17 10 18 31 3 5

Cardiovascular Death According to the Treatment Groups 1. 0 Log Rank Test, P = 0.0037 HR (95 CI): 0.10 (0.01 0.79) 0. 8 0. 6 0. 4 0. 2 Aspirin Group Non Aspirin Group Nonaspirin Group (n) Aspirin Group 12 (n) 0 0 1 2 3 4 5 Year 12 77 62 12 12 20 10 11 11 65 59 11 10 17 95 8 18 30 1 31 54 s

Subgroup Analysis Events, No./Total No. Age, y Aspirin Group Nonaspirin Group Hazard Ratio (95 CI) 65 45/719 59/644 0.68 (0.46 0.99) <65 23/543 27/633 1.0 (0.57 1.70) Favors Aspirin Favors No Aspirin Gender Male 40/706 51/681 0.74 (0.49 1.12) Female 28/556 35/596 0.88 (0.53 1.44) Hypertensive Status Hypertensive 49/742 55/731 0.88 (0.60 1.30) Normotensive 19/520 31/546 0.64 (0.36 1.13) Lipid Status Dyslipidemia 38/680 43/665 0.88 (0.57 1.37) Normolipidemia 30/582 43/612 0.71 (0.45 1.14) 0.3 1.0 Hazard Ratio (95 CI) 2.0

Total Atherosclerotic Events According to the Treatment Groups: Subgroup Aged 65 Years or Older 1 2 1 0 8 Log Rank Test, P = 0.047 HR (95 CI): 0.68 (0.46 0.99) 6 4 2 Aspirin Group Nonaspirin Group Nonaspirin Group (n) Aspirin Group 7 (n) 0 0 1 2 3 4 5 Year 6 6 5 5 3 7 s 4 16 86 56 94 37 41 28 25 31 65 7

Adverse Events, Bleeding No difference between aspirin group (10 patients) and non aspirin group (7 patients) for composite of hemorrhagic stroke and severe GI bleeding 4 cases of severe gastrointestinal (GI) bleeding that required transfusion in aspirin group 6 hemorrhagic strokes (1 fatal) in aspirin group and 7 hemorrhagic strokes (4 fatal) in nonaspirin group

Wait for additional data

Ongoing Trials other studies in the works 1 ASCEND A Study of Cardiovascular Events in Diabetes aiming for 10000 pt, diabetes, age > 40, no CVD to provide more information on the role of ASA for the prevention of heart attacks, strokes among apparently healthy people with diabetes 2 ACCEPT D Aspirin and simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes aiming for 5170 pt, diabetes, LDL > 100, no CVD evaluate efficacy of ASA in primary prevention of major CV events in patients with diabetes

Secondary What dose Prevention of aspirin?

Aspirin Evidence: Secondary Prevention Antithrombotic Trialist Collaboration Effect of aspirin on Death, MI and stroke Odds Reduction Acute MI Acute CVA Prior MI Prior CVA/TIA Other high risk CVD (e.g. unstable angina, heart failure) PAD (e.g. intermittent claudication) High risk of embolism (e.g. Afib) 0. 0. 1. 1. All trials 0Antiplatelet 5 better 0 5 Control better 2. 0 Antithrombotic Trialist Collaboration. BMJ 2002;324:71

Aspirin Responsiveness? Not specific test Not specific test Not specific test Not specific test Not specific test Ferguson, Tex Heart Inst J. 2008;35(3):313 20

Rate of low responders to Aspirin 5 Adapted from Lordkipanidze et al.

Overestimation of Aspirin Resistance: Key Role of Compliance Tantry et al., JACC, 2005

ASPECT study and FIASCO study n=120 Gurbel et al. Circulation 2007;115:3156 3164 Cuisset et al. Thromb Res. 2008 Nov 4.

ASPECT study: Subgroup of diabetics n=30 n=90 Di Chiara et al. Diabetes 2007;56:3014 3019

Aspirin Evidence: Secondary Prevention Antithrombotic Trialist Collaboration 500 1500 mg 34 19 160 325 mg 19 26 75 150 mg 12 32 <75 mg 3 13 Aspirin Evidence: Dose and Efficacy Aspirin Dose No. of Trials () Odds Ratio for Vascular Events Any aspirin 65 23 P<.0001 0 0.5 1.0 1.5 2.0 Antiplatelet Better Antiplatelet Worse Antithrombotic Trialist Collaboration. BMJ 2002;324:71 86

CURE STUDY: Effect of aspirin dose in ACS CURE CV death, MI, stroke, refractory angina Major bleeding 2 5 2 0 1 5 1 0 5 0 18. 2 17. 16. 2 3 <100 mg n=53 20 15. 7 20. 7 17. 4 >200 mg n=41 10 6 5 4 3 2 1 0 1. 9 Aspirin + Placebo Aspirin + Clopidogrel P<0.00 1 3. 0 <100 mg n=53 20 2. 8 3. 4 101-199mg n=31 09 101-199mg n=31 09 3. 7 4. 9 >200 mg n=41 10

CURRENT OASIS 7: Effect of aspirin dose in ACS Death/MI/Stroke at 30 days Major Bleeding at 30 days

Is clopidogrel What dose better of aspirin? than aspirin?

Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) Trial 1 6 Cumulative Event Rate () (MI, Ischemic Stroke or Vascular Death) 1 2 8 4 0 19,185 patients with ischemic CVA, MI, or PAD randomized to daily aspirin (325 mg) or clopidogrel (75 mg) for 2 years 0 3 6 9 1 1 1 2 2 2 2 Months 5 of 8follow up 1 4 7 *ITT analysis CAPRIE Steering Committee. Lancet 1996; 348: 1329 39. p = 0.043, n = 19,185 3 0 AS 8.7* 5.8 A Overall relative risk reductio Clopidogre n l 3 3 5.3 3 6

Not really stable patients Population

Conclusion Primary Prevention No data in high risk patients Contradiction in Diabetics => Wait for additional data Secondary prevention Educate patient on importance of compliance Increase aspirin dose => no benefit except maybe in diabetics? (...increasing the dose of aspirin does not enhance COX 1 inhibition) Switch to other anti platelet medications (?) (...no evidence that switching to alternative treatment strategies improves outcomes)

Thank you!!!