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Meta-Analysis
. 2012 Sep 12;2012(9):CD001342.
doi: 10.1002/14651858.CD001342.pub3.

Vitamin K antagonists versus antiplatelet therapy after transient ischaemic attack or minor ischaemic stroke of presumed arterial origin

Els Llm De Schryver  1 , Ale Algra, L Jaap Kappelle, Jan van Gijn, Peter J Koudstaal
Affiliations
Meta-Analysis

Vitamin K antagonists versus antiplatelet therapy after transient ischaemic attack or minor ischaemic stroke of presumed arterial origin

Els Llm De Schryver et al. Cochrane Database Syst Rev. .

Abstract

Background: People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with vitamin K antagonists is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy.

Objectives: To compare the efficacy and safety of vitamin K antagonists and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin.

Search methods: We searched the Cochrane Stroke Group Trials Register (last searched 15 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September 2011) and EMBASE (2008 to September 2011). In an effort to identify further relevant trials we searched ongoing trials registers and reference lists. We also contacted authors of published trials for further information and unpublished data.

Selection criteria: Randomised trials of oral anticoagulant therapy with vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus antiplatelet therapy for long-term secondary prevention after recent transient ischaemic attack or minor ischaemic stroke of presumed arterial origin.

Data collection and analysis: Two review authors independently selected trials, assessed trial quality and extracted data.

Main results: We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21).

Authors' conclusions: For the secondary prevention of further vascular events after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications.

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Conflict of interest statement

The authors were all members of the Executive Committee of ESPRIT 2007, the European/Australian Stroke Prevention in Reversible Ischaemia Trial. All authors, except Els de Schryver, were members of the Executive Committee of SPIRIT 1997, the Stroke Prevention in Reversible Ischaemia Trial.

Ale Algra is employed by the University Medical Center Utrecht. He has received several grants for cerebrovascular research from granting bodies such as the Netherlands Heart Foundation, Nederlandse HersenStichting, TromboseStichting Nederland, Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO, Netherlands Organisation for Scientific Research) and Nederlandse Organisatie voor Gezondheidsonderzoek en Zorginnovatie (ZonMW, Netherlands Organisation for Health Research and Development). In the last five years he has received speaker fees and travel expenses from Boehringer Ingelheim and Sanofi. He is one of the principal investigators of ESPRIT, the European/Australian Stroke Prevention in Reversible Ischaemia Trial, a trial that was run independently of any pharmaceutical company. After completion and full analysis of ESPRIT, the study group accepted financial support from Boehringer Ingelheim for post hoc exploratory analyses of the ESPRIT trial data in 2006. For this purpose a contract was signed in which we negotiated complete scientific freedom.

Jaap Kappelle has, in the past five years, received speaker and consulting honoraria from Boehringer Ingelheim and Bayer.

Jan van Gijn was principal investigator (with Ale Algra) of the SPIRIT Study (anticoagulants versus aspirin) ‐ no commercial interest.

Figures

1.1
1.1. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 1 The composite vascular death, non‐fatal stroke, non‐fatal myocardial infarction or major bleeding complication.
1.2
1.2. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 2 All death.
1.3
1.3. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 3 Vascular death.
1.4
1.4. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 4 Vascular death or non‐fatal stroke.
1.5
1.5. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 5 Vascular death, non‐fatal stroke or non‐fatal myocardial infarction.
1.6
1.6. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 6 Recurrent ischaemic stroke.
1.7
1.7. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 7 Recurrent ischaemic stroke or intracranial haemorrhage.
1.8
1.8. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 8 Death or dependent at end of follow‐up.
1.9
1.9. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 9 Major bleeding complication.
1.10
1.10. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 10 Fatal intracranial or extracranial haemorrhage.
1.11
1.11. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 11 Intracranial haemorrhage, fatal or non‐fatal.
1.12
1.12. Analysis
Comparison 1 Vitamin K antagonists versus antiplatelet therapy, Outcome 12 Major extracranial haemorrhage.
2.1
2.1. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 1 The composite vascular death, non‐fatal stroke, non‐fatal myocardial infarction or major bleeding complication.
2.2
2.2. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 2 All death.
2.3
2.3. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 3 Vascular death.
2.4
2.4. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 4 Vascular death or non‐fatal stroke.
2.5
2.5. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 5 Vascular death, non‐fatal stroke or non‐fatal myocardial infarction.
2.6
2.6. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 6 Recurrent ischaemic stroke.
2.7
2.7. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 7 Recurrent ischaemic stroke or intracranial haemorrhage.
2.8
2.8. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 8 Death or dependent at end of follow‐up.
2.9
2.9. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 9 Major bleeding complication.
2.10
2.10. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 10 Fatal intracranial or extracranial haemorrhage.
2.11
2.11. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 11 Intracranial haemorrhage, fatal or non‐fatal.
2.12
2.12. Analysis
Comparison 2 Vitamin K antagonists versus antiplatelet therapy (concealed randomised trials), Outcome 12 Major extracranial haemorrhage.
3.1
3.1. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 1 The composite vascular death, non‐fatal stroke, non‐fatal myocardial infarction or major bleeding complication.
3.2
3.2. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 2 All death.
3.3
3.3. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 3 Vascular death.
3.4
3.4. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 4 Vascular death or non‐fatal stroke.
3.5
3.5. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 5 Vascular death, non‐fatal stroke or non‐fatal myocardial infarction.
3.6
3.6. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 6 Recurrent ischaemic stroke.
3.7
3.7. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 7 Recurrent ischaemic stroke or intracranial haemorrhage.
3.8
3.8. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 8 Death or dependent at end of follow‐up.
3.9
3.9. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 9 Major bleeding complication.
3.10
3.10. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 10 Fatal intracranial or extracranial haemorrhage.
3.11
3.11. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 11 Intracranial haemorrhage, fatal or non‐fatal.
3.12
3.12. Analysis
Comparison 3 Vitamin K antagonists versus aspirin only, Outcome 12 Major extracranial haemorrhage.
4.1
4.1. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 1 The composite vascular death, non‐fatal stroke, non‐fatal myocardial infarction or major bleeding complication.
4.2
4.2. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 2 All death.
4.3
4.3. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 3 Vascular death.
4.4
4.4. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 4 Vascular death or non‐fatal stroke.
4.5
4.5. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 5 Vascular death, non‐fatal stroke or non‐fatal myocardial infarction.
4.6
4.6. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 6 Recurrent ischaemic stroke.
4.7
4.7. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 7 Recurrent ischaemic stroke or intracranial haemorrhage.
4.8
4.8. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 8 Death or dependent at end of follow‐up.
4.9
4.9. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 9 Major bleeding complication.
4.10
4.10. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 10 Fatal intracranial or extracranial haemorrhage.
4.11
4.11. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 11 Intracranial haemorrhage, fatal or non‐fatal.
4.12
4.12. Analysis
Comparison 4 Vitamin K antagonists versus aspirin, including intracranial artery stenosis, Outcome 12 Major extracranial haemorrhage.
See this image and copyright information in PMC

Update of

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