1. Antithrombotic Trialists’ Collaboration An updated collaborative overview of randomised trials of antiplatelet therapy among high-risk patients

2. Antithrombotic Trialists’ Collaboration Definitions: “Serious vascular event” : combined outcome of non-fatal myocardial infarction, non-fatal stroke, or death from a vascular (or unknown) cause “High-risk” : risk of a serious vascular event more than about 3% per annum because of previous occlusive disease or a predisposing condition

3. Antithrombotic Trialists’ Collaboration: VASCULAR EVENTS CategoryAPTCTRLReduction Prior MI13.5%17.0%25%±4 Acute MI10.4%14.2%30%±4 Prior stroke/TIA17.8%21.4%22%±4 Acute stroke8.2%9.1%11%±3 Other high risk8.0%10.2%26%±3 All except 11.7%14.8%25%±2 acute stroke All trials10.7%13.2%22%±2 (P<0.0001) 1.00.50.01.52.0

4. Antithrombotic Trialists’ Collaboration: VASCULAR EVENTS CategoryAPTCTRLReduction Prior MI13.5%17.0%25%±4 Acute MI10.4%14.2%30%±4 Prior stroke/TIA17.8%21.4%22%±4 Acute stroke 8.2%9.1%11%±3 Other high risk* CAD6.2%8.9%37%±5 Embolic risk13.5%16.8%26%±7 PAD5.8%7.1%23%±8 Other11.3%12.6%13%±7 All trials10.7%13.2%22%±2 1.00.50.01.52.0

5. Benefit per 1000(SE): A13.5%A10.4%A17.8%A8.2%A8.1%C21.4%C14.2%C17.0%C9.1%C10.2% 0% 10% 20% Prior MI Acute MI Prior stroke/TIA Acute stroke Other high risk CATEGORY: A = Antiplatelet therapy C = Control Average duration: 27 m 36(5) 1m 38(5) 29 m 36(6) 0.7 m 9(3) 22 m 22(3) P-value: <0.0001<0.0001 <0.0001 0.0009<0.0001 Antithrombotic Trialists’ Collaboration: Absolute effects on VASCULAR EVENTS

6. Antithrombotic Trialists’ Collaboration: NON-FATAL MYOCARDIAL INFARCTION CategoryAPTCTRLReduction Prior MI4.7%6.5%30%±6 Acute MI1.0%2.3%55%±8 Prior stroke/TIA1.7%2.3%31%±9 Acute strokeNo data Other high risk2.7%3.8%32%±5 All trials2.6%3.7%34%±3 (P<0.0001) 1.00.50.01.52.0

7. Antithrombotic Trialists’ Collaboration: NON-FATAL STROKE CategoryAPTCTRLReduction Prior MI0.9%1.4%39%±11 Acute MI0.3%0.6%40%±17 Prior stroke/TIA8.3%10.8%25%±5 Acute stroke2.1%2.6%18%±6 Other high risk1.5%2.2%30%±7 All trials2.6%3.5%25%±3 (P<0.0001) 1.00.50.01.52.0

8. Antithrombotic Trialists’ Collaboration: VASCULAR DEATH CategoryAPTCTRLReduction Prior MI8.0%9.4%15%±5 Acute MI9.1%11.4%22%±4 Prior stroke/TIA8.0%8.7%11%±5 Acute stroke6.1%6.5%8%±4 Other high risk4.5%5.3%17%±4 All trials6.8%7.6%15%±2 (P<0.0001) 1.00.50.01.52.0

9. Antithrombotic Trialists’ Collaboration: ANY DEATH CategoryAPTCTRLReduction Prior MI9.2%10.3%12%±5 Acute MI9.2%11.5%22%±4 Prior stroke/TIA11.3%12.8%14%±5 Acute stroke6.1%6.5%8%±4 Other high risk5.9%6.7%15%±4 All trials7.7%8.8%14%±2 (P<0.0001) 1.00.50.01.52.0

10. A 471 471 9 984 (4.7%) A 83 83 9 222 (0.9%) A 799 799 9 984 (8.0%) A 914 914 9 984 (9.2%)C 939 939 10 022 (9.4%)C 129 129 9 250 (1.4%) C 654 654 10 022 (6.5%) C 1 035 1 035 10 022 (10.3%) 0% 5% 10% Non-fatalreinfarction Non-fatalstroke Vasculardeath A = Antiplatelet therapy (mean 2 years) C = Control Benefit per 1000 patients (SE) 2P <0.0001 0.0020.00060.02 12 (5) 18 (3) 5 (1) 14 (4) Any death Absolute effects in patients with PREVIOUS MYOCARDIAL INFARCTION

11. A 95 95 9 534 (1.0%) A 32 32 9 300 (0.3%) A 883 883 9 658 (9.1%) A 886 886 9 658 (9.2%) C 1104 11049644(11.4%) C 54 54 9 291 (0.6%) C 215 215 9 521 (2.3%) C 1 112 1 112 9 644 (11.5%) 0% 5% 10% Non-fatalreinfarction Non-fatalstroke Vasculardeath A = Antiplatelet therapy (mean 1 month) C = Control Benefit per 1000 patients (SE) 2P <0.00010.02 <0.0001 <0.0001 24 (4) 13 (2) 2 (1) 23 (4) Any death Absolute effects in patients with ACUTE MYOCARDIAL INFARCTION

12. A 191 191 11 310 (1.7%) A957 11 493 (8.3%) A 915 915 11 493 (8.0%) A 1 303 1 303 11 493 (11.3%) C 1 003 1 003 11 527 (8.7%) C 1 248 11 527 (10.8%) C 261 261 11 338 (2.3%) C 1 475 11 527 (12.8%) 0% 5% 10% Non-fatalmyocardialinfarctionNon-fatalstrokerecurrence Vasculardeath A = Antiplatelet therapy (mean 3 years) C = Control Benefit per 1000 patients (SE) 2P 0.0009 <0.00010.04 0.002 15 (5) 6 (2) 25 (5) 7 (4) Any death Absolute effects in patients with PREVIOUS STROKE or TIA

13. A432 20 238 (2.1%) A 1 238 1 238 20 418 (6.1%) A 1 238 1 238 20 418 (6.1%) C 1 335 1 335 20 403 (6.5%) C 522 522 20 220 (2.6%) C 1 335 1 335 20 403 (6.5%) 0% 5% 10% Non-fatalmyocardialinfarctionNon-fatalstrokerecurrence Vasculardeath A = Antiplatelet therapy (mean 3 weeks) C = Control Benefit per 1000 patients (SE) 2P 0.0030.05 0.05 5 (2) 4 (2) 5 (2) Any death Absolute effects in patients with ACUTE STROKE (presumed ISCHAEMIC) Notrecorded

14. Antithrombotic Trialists’ Collaboration Effects on VASCULAR EVENTS in patients with CORONARY ARTERY DISEASE CategoryAPTCTRLReduction Unstable angina8.0%13.3%46%±7 Post-CABG4.8%4.7%4%±14 Post-PTCA2.7%5.5%53%±14 Stable angina/CAD9.9%14.1%33%±9 Heart failure6.1%10.3%41%±56 All high-risk patients 22%±2 (P<0.0001) 1.00.50.01.52.0

15. Antithrombotic Trialists’ Collaboration Effects on VASCULAR EVENTS in patients at HIGH RISK OF EMBOLISM CategoryAPTCTRLReduction Atrial fibrillation15.3%18.4%24%±9 Valve disease18.0%18.0%0%±19 Valve surgery7.6%13.2%45%±12 All high-risk patients 22%±2 (P<0.0001) 1.00.50.01.52.0

16. Antithrombotic Trialists’ Collaboration Effects on VASCULAR EVENTS in patients with PERIPHERAL ARTERIAL DISEASE CategoryAPTCTRLReduction Intermittent6.4%7.9%23%±9 claudication Peripheral graft5.4%6.5%22%±16 Peripheral2.5%3.6%29%±35 angioplasty All high-risk patients 22%±2 (P<0.0001) 1.00.50.01.52.0

17. Antithrombotic Trialists’ Collaboration Effects on VASCULAR EVENTS in patients with OTHER HIGH-RISK CONDITIONS CategoryAPTCTRLReduction Haemodialysis2.9%4.9%41%±16 Diabetes15.7%16.7%7%±8 Carotid disease10.6%12.8%19%±22 All high-risk patients 22%±2 (P<0.0001) 1.00.50.01.52.0

18. Risks of serious bleeding with antiplatelet therapy Intracranial bleeds are increased by about a quarter, and extracranial bleeds by about a halfIntracranial bleeds are increased by about a quarter, and extracranial bleeds by about a half Proportional increase in risk of each type of bleeding is similar in all high-risk patientsProportional increase in risk of each type of bleeding is similar in all high-risk patients

19. Antithrombotic Trialists’ Collaboration Aspirin vs control: effect of dose Aspirin doseASACTRLReduction 500-1500mg daily14.5%17.2%19%±3 160-325mg daily11.5%14.8%26%±3 75-150mg daily10.9%15.2%32%±6 <75 mg daily17.3%19.4%13%±8 Any aspirin dose12.9%16.0%23%±2 (P<0.0001) 1.00.50.01.52.0

20. Antithrombotic Trialists’ Collaboration Higher vs lower doses of aspirin ComparisonRegimen 1Regimen 2Reduction Asp 500-1500 14.1%14.5%3%±10 vs75-325mg daily Asp  75 vs14.2%13.2%-8%±10 <75mg daily Higher dose vs14.1%13.8%-3%±7 lower dose 1.00.50.01.52.0

21. Antithrombotic Trialists’ Collaboration Other antiplatelet drugs vs aspirin ComparisonAPTAspRedn P-value Sulphinpyrazone16.2%13.1%-18%±19NS Triflusal10.1%10.9%7%±12NS Ridogrel9.6%12.2%26%±18NS Dipyridamole16.7%16.5%-2%±9NS Indobufen5.3%4.1%-29%±29NS Ticlopidine 21.1% 23.2%12%±7NS Clopidogrel10.1%11.1%10%±40.03 Other antiplatelet1.3%1.4%6%±45NS 1.00.50.01.52.0

22. Antithrombotic Trialists’ Collaboration Aspirin plus another antiplatelet vs aspirin ComparisonAPTAspReduction Asp plus11.8%12.4%6%±6 dipyridamole Asp plus13.4%17.3%26%±20 sulphinpyrazone Asp+ ticlopidine4.8%5.9%20%±24 Asp + iv IIb/IIIa- 9.9%11.8%19%±4 inhibitor 1.00.50.01.52.0

23. Antithrombotic Trialists’ Collaboration Conclusions Aspirin (or another antiplatelet drug) prevents serious vascular events in a wide range of high-risk patients, including people with intermittent claudication, stable angina, and  if oral anticoagulants are unsuitable  atrial fibrillation Low-dose aspirin (75-150mg daily) is as effective as higher aspirin doses for long-term use Clopidogrel is an effective alternative in patients with a contraindication to aspirin In some clinical circumstances, adding a second antiplatelet drug (e.g. clopidogrel or a GPIIb/IIIa antagonist) to aspirin may produce additional benefits