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Acute Antithrombotic Treatment includes
- Deep vein thrombosis (DVT) and pulmonary embolism (PE) prophylaxis
- Anticoagulation
- Aspirin
The role of antithrombotic therapy in acute stroke is to prevent recurrent strokes and further vascular events.
Administration of heparin or low-molecular-weight heparin, in bedridden patients after stroke, is recommended only
to reduce the number of DVTs and subsequent pulmonary embolism (PE) and only after 24 hours following thrombolysis.
However, there is a risk of intracranial bleeding. Acute treatment with aspirin can be started acutely or,
following thrombolysis, 24 hours later. Studies in Cologne have suggested that in patients already receiving
ASA treatment, intracranial bleeding is more likely associated with thrombolysis given later than 3 hours
following acute stroke. Caution is required.
Anticoagulation for DVT and PE Prophylaxis
- Some form of DVT and PE prophylaxis is necessary
- Mechanical
- Compression stockings not established for stroke patients but are relatively safe
- Anticoagulants
- Heparin treatment reduces the occurrence of DVT but is associated with an increased risk of haemorrhage
- In patients with particularly high risk of DVT, prophylactic treatment with heparin should be initiated early
All stroke patients not able to move around independently must have some form of DVT and PE prevention. This is as
important in ischaemic as in haemorrhagic stroke. Full-dose heparin is seldom indicated for prevention but may be
used after DVT or PE has occurred. Prevention of DVT and PE in all stroke patients is paramount and should be employed
from the time of admission unless otherwise contraindicated.
References:
Adams et al. Stroke 1994; 25 (9): 1901-1914.
Coull et al. Stroke 2002; 33 (7) : 1934-1942
Antithrombic Trialists‘ Collaboration Brit Med J 2002; 324 (7329): 71-86.
 
Therapeutic Anticoagulation
- Unfractioned heparin
- no formal trial available testing standard i.v. heparin
- IST (International Stroke Trial) showed no net benefit for s.c. heparin treated patients because of increased risk of intracranial haemorrhage
- Low-molecular-weight heparins
- No benefit on stroke outcome for low-molecular- heparin treated patients
- Heparinoid (Orgaran)
There are a few indications for therapeutic anticoagulation although the evidence to support them is weak. The list
includes sinus thrombosis, some acquired and hereditary coagulopathies with a high risk of systemic thrombosis
including in the brain. Also, here the therapy is targeted for prevention of the progression of stroke and of
recurrent events, not for the therapy of the ongoing event.
Early anticoagulation has been used frequently in the treatment after acute ischaemic stroke. None of the trials
that have been done in the past years have supported the idea that early heparin influences the outcome after
ischaemic stroke or may even reduces the number of recurrent strokes. However, few physicians will risk avoiding the use of heparin either prophylactically or therapeutically if they perceive a clinical need for acute anticoagulation.
- Unproven indications for heparin treatment after stroke
- Stroke due cardiac emboli with high risk of re- embolism (mechanical prosthetic valves, atrial fibrillation (AF), MI with mural thrombi, left atrial thrombosis)
- Venous sinus thrombosis
- Coagulopathies (protein C and S deficiency, antiphospholipid syndrome, Activated Protein C (APC) resistance)
- Symptomatic dissection of extracranial arteries
- Symptomatic extra- and intracranial cranial stenoses (tight carotid stenosis before CE (cardiologic embolism), crescendo transient ischaemic attacks (TIAs) or stroke in progression, basilary artery dolichoectasia)
Initiation of heparin has not been shown to improve the outcome of patients with acute stroke. The same applies
to the use of heparin in patients with AF and acute stroke or cardiogenic brain embolism, although no randomized
controlled trials big enough to prove or disprove this have been done. However, parenteral heparin is the only anticoagulant drug that can bridge the gap before oral anticoagulation becomes effective. Oral anticoagulation has been shown to be as effective as aspirin in preventing second stroke.
| EUSI Recommendations |
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| 1. |
There is no indication for the general use of heparin, low- molecular-weight heparins or heparinoids as an acute therapeutic measure after ischaemic stroke (Level I) |
| 2. |
Full dose heparin may be used in cerebral venous thrombosis (Level II) and in selected indications such as patients with high- risk cardiac sources, cervical artery dissection, or high-grade arterial stenosis prior to surgery (Level IV) |
Most investigators now agree that heparin is not and never will be a standard therapy for all
stroke subtypes, but high-risk patients (such as patients with stroke associated with AF, for example), should
be considered separately.
References:
IST Investigators. Lancet 1997; 349 (9065): 1569-158.
Toast Investigators. JAMA 1998; 279 (16): 1265-1272.
SPIRIT Investigators. Ann Neurol 1997; 42 (6): 857-865.
EUSI Recommendations. 2002, www.eusi-stroke.com
Acute Treatment: Platelet Inhibitors
Aspirin (acetyl salicylic acid)
- Tested in large RCT in acute (< 48 hours) stroke
- Significant reduction in death and dependency (NNT[number needed to treat] 70) and recurrence of stroke (NNT 140)
- In a combined analysis of the International Stroke Trial and the Chinese Acute Stroke Trial, the reduction in death and dependency during the first 2 weeks was 1% (NNT 100)
Stroke is a common and often disastrous condition so even small improvements matter. Aspirin is cheap and can
improve the outcome of acute stroke patients marginally. Therapy can be initiated without CT but the use of
aspirin may be dangerous in patients with acute bleeding disorders. Because the mode of action of aspirin is
prevention and not salvation from ischaemic injury, its use must be balanced against the risk that it will
induce or worsen haemorrhages.
Ticlopidine and clopidogrel
- Not tested in acute stroke
Glycoprotein (GP) IIb-IIIa antagonists
- Tested in a Phase IIa trial with encouraging results
- Abciximab appears to be safe when administered up to 24 hours after stroke onset, and might improve functional outcome
No antiplatelet agents other than aspirin have been tested in acute stroke. Some have a place in connection with
angioplasty and stenting in AMI but there are no data in acute stroke and they are contraindicated for the first
24 hours after thrombolysis in acute stroke. GP IIb-IIIa antagonists, either with or after stroke thrombolysis,
are under investigation and they may have a role of their own in acute ischaemic stroke but their use must await
the results of the ongoing trials.
EUSI-Recommendations
- Aspirin 100-300 mg/day should be given with ischaemic stroke within 48 hours after stroke onset (Level I)
- If thrombolytic therapy is planned, no aspirin should be given
- Aspirin is not recommended before 24 hours after thrombolytic therapy
ASA is the best-studied medical therapy used for stroke prevention. Many meta-analyses with trials involving patients
allocated to antplatelet therapy, have shown that the most effective dose of ASA is 100-300 mg/day. ASA should be
given to stroke patients only when no thrombolytic therapy is planned, and then, only between 24 and 48 hours after
stroke onset. However, prior aspirin treatment is not a contra-indication for treatment with rt-PA, only attracting a need for caution.
References:
IST Investigators. Lancet 1997; 349 (9065): 1569-158.
CAST Investigators. Lancet 1997; 349 (9066): 1641-1649.
Antithrombotic Trialists' Collaboration. Brit Med J 2002; 324 (7329): 71-86
AbBEST Investigators. Stroke 2000; 31 (3): 601-609.
EUSI Recommendations. 2002, www.eusi-stroke.com |
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© 2005 Boehringer Ingelheim GmbH, Germany. All rights reserved.
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