Mikael Mazighi Service de neurologie and Centre d’accueil et

de traitement de l’attaque cérébrale Hôpital Bichat, Paris

Prévalence hémorragies cérébrales liées aux AVK

Flaherty ML, et al. Neurology. 2007

• 4052 patients avec ACFA, anticoagulant ou aspirine • Patients avec anticoagulant ont moins d’AVC (2.4 vs 4.5 ev pour 100 patient-années; [HR], 0.55; 95%, 0.43-0.71), • 1000 patients traités pour ACFA pdt 1 an avec anticoagulant prévient 23 infarctus cérébraux et cause 9 hémorragies majeures

Anticoagulant & Avc cardioembolique

van Walraven C JAMA. 2002 :2441-8.

van Walraven C JAMA. 2002 :2441-8.

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

Infarctus cérébral (HR, 0.48; 95% CI, 0.37-0.63)

AVK

Aspirine

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

Hémorragies majeures (2.2 vs 1.3 evts pour 100 patient-années; HR, 1.71; 1.21-2.41)

AVK Aspirine

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

van Walraven C JAMA. 2002 :2441-8.

AVK versus aspirine

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

by guest on December 3, 2011jama.ama-assn.orgDownloaded from

Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

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Figure 1. Outcomes Survival Curves

No. at Risk

Oral Anticoagulants

Aspirin

No. at Risk

Oral Anticoagulants

Aspirin

0.25!2 = 14.7, P<.0010.20

0.15

0.10

0.05

00

1939

2113

1

1409

1514

829

881

432

165

140

348

352

Year

Pro

porti

onW

ith E

vent

Cardiovascular Events

2113

0.25!2 = 21.7, P<.0010.20

0.15

0.10

0.05

0

Pro

porti

onW

ith E

vent

All Strokes

1939 1413

1525

831

890

163

145

351

358

!2 = 9.5, P = .02

0

1939

2113

1

1413

1553

821

925

432

158

146

347

365

Year

Major Bleeding

!2 = 29.5, P<.001

Ischemic Strokes

1939

2113

1415

1526

833

893

165

145

352

358

OralAnticoagulants

Aspirin

!2 = 0.6, P = .44

0

1939

2113

1

1434

1569

844

938

432

168

153

360

377

Year

Death

!2 = 2.7, P = .19

Hemorrhagic Strokes

1939

2113

1432

1568

842

935

166

153

359

376

In each plot, the horizontal axis represents time in years. The P value is a log-rank statistic. All strokes included ischemic and hemorrhagic events. Cardiovascular eventsincluded ischemic strokes, myocardial infarctions, systemic emboli, and vascular death. Major bleeding events included intracranial and major systemic bleeds.

Figure 2. Relationship of Therapy With Outcomes in Individual Trials

0 1 3 42Hazard Ratio

Major BleedingP = .87

Ischemic StrokesP = .88

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

0 1 3 42Hazard Ratio

Cardiovascular EventsP = .96

AFASAK 1EAFTPATAFSPAF 2AFASAK 2SPAF 3

Overall

All StrokesP = .83

0 1 3 42Hazard Ratio

DeathP = .99

Hemorrhagic StrokesP = .98

For each study, the relative effect of oral anticoagulants vs aspirin (with or without low-dose warfarin) is presented for all 6 outcomes as a hazard ratio. Hazard ratiosbelow 1 indicate that oral anticoagulant decreases the risk of the event. Hazard ratios whose 95% confidence interval (error bars) excludes 1 are statistically significantat the 5% level. Because hemorrhagic strokes were uncommon events, a hazard ratio could not be estimated for each study individually. The P value for the DerSimonianand Laird Q statistic, as a measure of heterogeneity, is presented for each outcome in the top right-hand corner. AFASAK indicates Atrial Fibrillation, Aspirin, Antico-agulation study2,3; EAFT, European Atrial Fibrillation Trial5; PATAF, Primary Prevention of Atrial Thromboembolism in patients with Nonrheumatic Atrial Fibrillation inPrimary Care4; SPAF, Stroke Prevention in Atrial Fibrillation studies.7,9

ORAL ANTICOAGULANTS AND ASPIRIN IN ATRIAL FIBRILLATION

©2002 American Medical Association. All rights reserved. (Reprinted) JAMA, November 20, 2002—Vol 288, No. 19 2445

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van Walraven C JAMA. 2002 :2441-8.

Contre indication: L’hémorragie cérébrale

Qureshi Lancet 2009

•  Hémorragies surviennent en cas de INR en zone thérapeutique

•  Age avancé et angiopathie amyloide =facteur d’ hémorragie associé à AVK

•  Aggravation dans les premières 24-48 heures ds 50% des cas

Rosand. Neurology 2000 Palareti Lancet 1996 Sjoblom Stroke 2001

•  Traitement anticoagulant (niveau d’anticoagulation) •  HTA •  Age •  Dialyse •  Antécédents d’AVC ou maladie cérébrovasculaire •  Angiopathie amyloide (hémorragie lobaire,

microsaignements) et leucoaraiose

Pengo V, et al. Thromb Haemost. 2001 418-22 Campbell et al. Arch Intern Med. 1996

Fan YH,et al. Stroke. 2003 Smith EE, et al. Neurology. 2002

VazquezE, et al Int J Cardiol. 2003

Facteurs de risque d’hémorragie

La  topographie  condi/onne  le  mécanisme  de  l’hémorragie  

hémorragie lobaire: risque de récidive de 4% patient-année

• Scanner: examen de débrouillage. Injection de PdC détecte saignement actif

• IRM: séquence écho de gradient, T2* pour microsaignement, certaines malformations vasculaires (cavernome) • Angiographie conventionelle: malformation vasculaire (anévrysme, malformation artério-veineuse, thrombose veineuse, vascularite)

Imagerie

Les  micro-­‐saignements  

Kumar et al Neurology 2010 Roob et al . Curr Opin Neurol. 2000 Feb;13(1):69-73

Dépots d‘hémosidérine = saignements antérieurs

Association entre microsaignement et maladie des petites

artères (HTA, angiopathie amyloide)

Microsaignements, risque hémorragique 9.3% vs 1.3%

Angiopathie amyloide

Angiopathie  amyloide  

Angiopathie amyloide

•  Angiopathie amyloide : dépôts de peptide amyloide-β et formation de microanévrysme, infiltrats inflammatoires, nécrose fibrinoide dans les capillaires, artérioles, artères de petits et moyen calibres des artères du cortex, cervelet méninges

•  Hémorragies parenchymateuses sporadiques intracerebrales, forme familliale chez jeune

•  Anomalies de la substance blanche

Rosand et al Neurology 2000 Rost et al Stroke 2008

Eléments clés

Type d’hémorragie

Age

Facteur de récidive

•  Dépend du risque de récidive événement thromboembolique, récidive d’hémorragie, état général du patient •  Faible risque d’infarctus cérébral: ACFA sans ATCD d’infarctus cérébral •  Risque élevé d’hémorragie: angiopathie amyloide (patients âgés avec hémorragie lobaire), altération des fonctions cognitives •  Risque thromboembolique très élevé: reprise AVK, 7-10 jours après hémorragie (Class IIb; Level of Evidence B, Nouvelle recommandation) •  Transformation hémorragique: continuer anticoagulation(Class IIb; Level of Evidence C).

Recommandations ASA, EUSI

•  Contre-indication aux traitements anti-thrombotiques en cas d’hémorragies aigues

•  Sous groupe de patient à haut risque d’événements thrombo-emboliques/faible risque de récidive hémorragique pourrait bénéficier d’une anticoagulation à long terme.

•  Reprise des AVK en cas de risque très élevé d’événement thrombo-embolique à 7–14 jours après la survenue d’hémorragie intracrânienne

Furie et al Stroke 2011 Qureshi Lancet 2009