Antithrombotic Trialists Collaboration

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Antithrombotic Trialists Collaboration

• An updated collaborative overview of randomised
  trials of antiplatelet therapy among high-risk
  patients

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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

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Antithrombotic Trialists Collaboration VASCULAR
EVENTS

• Category APT CTRL Reduction
• Prior MI 13.5 17.0 254
• Acute MI 10.4 14.2 304
• Prior stroke/TIA 17.8 21.4 224
• Acute stroke 8.2 9.1 113
• Other high risk 8.0 10.2 263
• All except 11.7 14.8 252
• acute stroke
• All trials 10.7 13.2 222
• (Plt0.0001)

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Antithrombotic Trialists Collaboration VASCULAR
EVENTS

• Category APT CTRL Reduction
• Prior MI 13.5 17.0 254
• Acute MI 10.4 14.2 304
• Prior stroke/TIA 17.8 21.4 224
• Acute stroke 8.2 9.1 113
• Other high risk
• CAD 6.2 8.9 375
• Embolic risk 13.5 16.8 267
• PAD 5.8 7.1 238
• Other 11.3 12.6 137
• All trials 10.7 13.2 222

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Antithrombotic Trialists Collaboration
Absolute effects on VASCULAR EVENTS
36(5)
Benefit per 1000(SE)
38(5)
36(6)
9(3)
22(3)
Average duration
27 m
1m
29 m
22 m
0.7 m
P-value
lt0.0001
lt0.0001
lt0.0001
0.0009
lt0.0001
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A Antiplatelet therapy
C Control
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A 13.5
A 10.4
A 17.8
A 8.2
A 8.1
C 21.4
C 14.2
C 17.0
C 9.1
C 10.2
0
CATEGORY
Acute MI
Prior
Acute
Other high
Prior MI
stroke/TIA
stroke
risk
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Antithrombotic Trialists Collaboration
NON-FATAL MYOCARDIAL INFARCTION

• Category APT CTRL Reduction
• Prior MI 4.7 6.5 306
• Acute MI 1.0 2.3 558
• Prior stroke/TIA 1.7 2.3 319
• Acute stroke No data
• Other high risk 2.7 3.8 325
• All trials 2.6 3.7 343
• (Plt0.0001)

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Antithrombotic Trialists Collaboration
NON-FATAL STROKE

• Category APT CTRL Reduction
• Prior MI 0.9 1.4 3911
• Acute MI 0.3 0.6 4017
• Prior stroke/TIA 8.3 10.8 255
• Acute stroke 2.1 2.6 186
• Other high risk 1.5 2.2 307
• All trials 2.6 3.5 253
• (Plt0.0001)

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Antithrombotic Trialists Collaboration VASCULAR
DEATH

• Category APT CTRL Reduction
• Prior MI 8.0 9.4 155
• Acute MI 9.1 11.4 224
• Prior stroke/TIA 8.0 8.7 115
• Acute stroke 6.1 6.5 84
• Other high risk 4.5 5.3 174
• All trials 6.8 7.6 152
• (Plt0.0001)

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Antithrombotic Trialists Collaboration ANY DEATH

• Category APT CTRL Reduction
• Prior MI 9.2 10.3 125
• Acute MI 9.2 11.5 224
• Prior stroke/TIA 11.3 12.8 145
• Acute stroke 6.1 6.5 84
• Other high risk 5.9 6.7 154
• All trials 7.7 8.8 142
• (Plt0.0001)

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Antithrombotic Trialists Collaboration Effects
on VASCULAR EVENTS in patients with CORONARY
ARTERY DISEASE

• Category APT CTRL Reduction
• Unstable angina 8.0 13.3 467
• Post-CABG 4.8 4.7 414
• Post-PTCA 2.7 5.5 5314
• Stable angina/CAD 9.9 14.1 339
• Heart failure 6.1 10.3 4156
• All high-risk patients 222
• (Plt0.0001)

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Antithrombotic Trialists Collaboration Effects
on VASCULAR EVENTS in patients at HIGH RISK OF
EMBOLISM

• Category APT CTRL Reduction
• Atrial fibrillation 15.3 18.4 249
• Valve disease 18.0 18.0 019
• Valve surgery 7.6 13.2 4512
• All high-risk patients 222
• (Plt0.0001)

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Antithrombotic Trialists CollaborationEffects
on VASCULAR EVENTS in patients with PERIPHERAL
ARTERIAL DISEASE

• Category APT CTRL Reduction
• Intermittent 6.4 7.9 239
• claudication
• Peripheral graft 5.4 6.5 2216
• Peripheral 2.5 3.6 2935
• angioplasty
• All high-risk patients 222
• (Plt0.0001)

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Antithrombotic Trialists Collaboration Effects
on VASCULAR EVENTS in patients with OTHER
HIGH-RISK CONDITIONS

• Category APT CTRL Reduction
• Haemodialysis 2.9 4.9 4116
• Diabetes 15.7 16.7 78
• Carotid disease 10.6 12.8 1922
• All high-risk patients 222
• (Plt0.0001)

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Risks of serious bleeding with antiplatelet
therapy

• Intracranial 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 patients

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Antithrombotic Trialists Collaboration Aspirin
vs control effect of dose

• Aspirin dose ASA CTRL Reduction
• 500-1500mg daily 14.5 17.2 193
• 160-325mg daily 11.5 14.8 263
• 75-150mg daily 10.9 15.2 326
• lt75 mg daily 17.3 19.4 138
• Any aspirin dose 12.9 16.0 232
• (Plt0.0001)

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Antithrombotic Trialists Collaboration Higher vs
lower doses of aspirin

• Comparison Regimen 1 Regimen 2 Reduction
• Asp 500-1500 14.1 14.5 310
• vs 75-325mg daily
• Asp ?75 vs 14.2 13.2 -810
• lt75mg daily
• Higher dose vs 14.1 13.8 -37
• lower dose

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Antithrombotic Trialists Collaboration Other
antiplatelet drugs vs aspirin

• Comparison APT Asp Redn P-value
• Sulphinpyrazone 16.2 13.1 -1819 NS
• Triflusal 10.1 10.9 712 NS
• Ridogrel 9.6 12.2 2618 NS
• Dipyridamole 16.7 16.5 -29 NS
• Indobufen 5.3 4.1 -2929 NS
• Ticlopidine 21.1 23.2 127 NS
• Clopidogrel 10.1 11.1 104 0.03
• Other antiplatelet 1.3 1.4 645 NS

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Antithrombotic Trialists Collaboration Aspirin
plus another antiplatelet vs aspirin

• Comparison APT Asp Reduction
• Asp plus 11.8 12.4 66
• dipyridamole
• Asp plus 13.4 17.3 2620
• sulphinpyrazone
• Asp ticlopidine 4.8 5.9 2024
• Asp iv IIb/IIIa- 9.9 11.8 194
• inhibitor

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Antithrombotic Trialists CollaborationConclusion
s

• 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