2. Anticoagulant Management In Ischemic Stroke
Mandy Binning, MD
Nick Hopkins MD
Elad Levy MD
Adnan Siddiqui MD, PhD
Dept of Neurosurgery
SUNY Buffalo

3. L. Nelson Hopkins, MD DISCLOSURES Consulting Fees
Abbott Vascular, Bard Peripheral Vascular, Boston Scientific Corporation, Micrus Endovascular Cordis, a Johnson & Johnson company
Grants/Contracted Research
Cordis, a Johnson & Johnson company, Boston Scientific Corporation, Micrus Endovascular
Honoraria
AccessClosure, Inc., Bard Peripheral Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson company, marketRx, Inc., Micrus Endovascular, Medsn
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
APW Holding, Inc., Boston Scientific Corporation, Magellan Spine Tech, Inc., MedFocus Accelerator Fund, Micrus Endovascular

4. L. Nelson Hopkins, MD
I disclose the following financial relationship(s):
Consultant, Honoraria- Abbott , BARD, Boston Scientific, Cordis, Micrus, Toshiba, Gore, Invatec
Financial Interest- AccessClosure, , Boston Scientific, Micrus,
Director- AccessClosure, Micrus
University Grants/Research Support-
Boston Scientific, Cordis, Micrus Toshiba

5. Small vessel occlusive
Causes of Stroke
15%
Hemorrhage
- Intracerebral
- Subarachnoid
85%
Infarction
20%
Large vesses Athero
Intracranial
Extracranial
20%
Cardioembolic
35% Others:
30% Cryptogenic
5% Other, unusual
25%
Small vessel occlusive
disease (lacunes)

6. Atherosclerosis: common sites

7. Causes of Stroke

8. Drug
Pentasaccharrides: Indirect Xa inhibitors - Foundaparinux, Idraparinux; Direct Xa inhibitor: Rivaroxaban, Apixaban
Clot formation
Direct Thrombin inhibitors: Hirudin, Bivalirudin, Argatraban
Oral: Ximelagatran, Dabigatran

9. Disagreements exist about :
Anticoagulants: Long history of use
Usefulness of emergency anticoag in debate
Disagreements exist about :
Best agent to administer
Route of administration
Use of a bolus dose to start treatment
Level of anticoagulation
Duration of treatment

10. Questions
Do antithrombotic agents reduce stroke-related morbidity and mortality?
Do antithrombotic agents reduce early stroke recurrence?
Do antithrombotic agents vary in efficacy according to stroke subtype?
Risk of Early Recurrent Embolism about 12% (range 2-22%) for cardiogenic embolic stroke
within 2 weeks if untreated.
Do antithrombotic agents reduce systemic thrombotic complications such as DVT/PE?
What are the risks of hemorrhage associated with antithrombotic treatment?

11. Do antithrombotic agents reduce stroke-related
Morbidity and mortality?

12. Platelet antiaggregants
Chinese Acute Stroke Trial (CAST) (RCT, double-blind, placebo-controlled)
21,106 patients
Aspirin 160 mg/day- within 48 hours of stroke onset.
Aspirin reduced early mortality rate (3.3 vs 3.9%; p=0.04)
CAST (Chinese Acute Stroke Trial) Collaboration Group. CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997;349:1641–1649.
International Stroke Trial (IST) –large prospective, randomized, but open-label trial of aspirin and SQ heparin 2 doses (5000 U/d or U/d)
Started within 48 hours of stroke.
19,436 patients
½ -randomized to aspirin mg/day.
½ avoid aspirin- SQ heparin or were instructed to avoid heparin.
Was not significant for patients death at 14 days- (heparin 9%, aspirin 9%; no heparin 9.3%, no aspirin 9.4%)
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.
Anticoagulants and Antiplatelet Agents in Acute Ischemic Stroke: Report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association Stroke Jul;33(7):

13. A combined analysis of these two trials:
aspirin (160 mg or 325 mg daily) given within 48 hours after ischemic stroke.
Small but statistically significant reduction of deaths or nonfatal strokes.
9 (+/-3) per 1000
(ARR- 0.9%; NNT- 111).
Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke: a combined analysis of 40,000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke 2000;31:1240–1249.

14. Unfractionated heparin
IST trial:
¼ Tx with SQ heparin IU BID
¼ Tx 12,500 IU BID
½ No heparin
In acute stroke- no reduction in mortality or morbidity with SQ heparin.
A subgroup with atrial fibrillation- did not demonstrate a benefit.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.
1986 a prospective, double-blind trial of dose-adjusted IV heparin (Class I)
225 patients
Stable carotid and VB stroke.
no difference in:
Death at 7 days
Functional activity at 7 days, 3 months, 1 year
6 months death or dependency
Mortality at one year was significantly increased in the unfractionated heparin-compared with the placebo group (heparin- 17 vs control-8; p<0.05).
Duke RJ, Bloch FG, Turpie AGG, et al. Intravenous heparin for the prevention of stroke progression in acute partial stable stroke: a randomized controlled trial. Ann Intern Med 1986;105:825–828.

15. A single-center, randomized study
Acute nonlacunar hemispheric infarctions
Adjusted IV heparin w/o an initial bolus dose vs saline within 3 hours of stroke onset
418 patients (208 on heparin)
In the heparin group:
Self-independent patients (38.9% versus 28.6%; P=0.025).
Fewer deaths (16.8% versus 21.9%;P=0.189),
More symptomatic brain hemorrhages (6.2% versus 1.4%; P=0.008)
More major extracerebral bleedings (2.9% versus 1.4%; P= 0.491).
(Stroke. 2005;36: )
A meta-analysis of the studies of heparin found no benefit from administration of the medication.
Gubitz G, Counsell C, Sandercock P, Signorini D. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2000;(2):

16. Low molecular weight heparins/heparinoids
A double-blind trial randomized, in Hong Kong hospitals (Class I).
308 patients
3 groups: placebo,
Nadroparin calcium at 4100 anti-Xa IU once daily,
4100 anti-Xa IU BID
3 months- No reduction in death or dependence
6 months- significant, dose-dependent benefit in the
drug-treated patients: good outcomes- 55% high-dose Nadroparin
45% in placebo.
Kay R, Sing Wong K, Yu YL, et al. Low-molecular-weight heparin for thetreatment of acute ischemic stroke. N Engl J Med 1995;333:1588–1593.
Fraxiparine in Ischemic Stroke Study
A large multicenter, randomized trial in a European population.
This result was not replicated.
Hommel M, FISS bis Investigators Group. Fraxiparine in Ischemic Stroke Study (FISS bis). Cerebrovasc Dis 1998;8(suppl 4):19A
The results for anti-Xa agents in acute ischemic stroke have not been consistent

17. TOAST Study- Trial of the Heparinoid ORG 10172 (danaparoid) in Acute Stroke
Randomized, double-blind, placebo-controlled trial (Class I).
1281 patients 36 US centers
Active arm received IV dose-adjusted danaparoid.
At 7 days- very favorable outcomes :
34% of danaparoid
28% of placebo
(p=0.01).
3 months- no significant difference in favorable outcomes.
Stroke secondary to large artery atherosclerosis was the only subgroup that showed benefit.
Publications Committee for the Trial of ORG in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG (Dsanaparoid), and outcome after acute ischemic stroke. JAMA 1998;279:1265–1272.

18. Heparin in Acute Embolic Stroke Trial (HAEST Study)
Prospective study (Class I).
Compared LMW heparin (Dalteparin), with aspirin
given within 30 hours of A. Fib associated stroke.
Patients taking aspirin had fewer second events.
Bleeding complications -higher with dalteparin
There were no statistically significant differences in death and physical dependency at 3 months
(66.1% in treated vs 64.8% in control).
Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group Heparin in Acute Embolic Stroke Trial. Lancet 2000;355:1205–1210.

19. TOPAS trial-Therapy of Patients with Acute Stroke.
A prospective, randomized, nonplacebo-controlled trial.
LMW heparin (Certoparin)- within 12 hours of acute
ischemic stroke
400 patients
4 treatment groups:
3000 U daily, 3000 U BID, 5000 U BID, 8000 U BID.
Serious bleeding complications was highest with largest dose of the LMW heparin
No benefit in stroke outcome (Short term or 3 mo.)
Diener HC, Ringelstein EB, von Kummer R, et al. Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin.
Results of the TOPAS Trial. Stroke 2001;32:22–29.

20. International Stroke Trial Panels of the AHA have concluded that the
uncertain or largely negative data about the utility & efficacy of heparin in the management of stroke.
Safety concern exists that urgent anticoagulation may lead to symptomatic ICH.
Guidelines for the Early Management of Adults With Ischemic Stroke, Stroke, 2007;38;

21. In patients within 48 hours of acute ischemic stroke onset
Abciximab,
unfractionated heparin
LMW heparins
Heparinoids
Have not been shown to reduce
mortality or morbidity.
Most trials have not demonstrated the efficacy of anticoagulation in improving
outcomes.
One relatively small trial -IV heparin shoed improve outcomes, when administered
within 3 hours of stroke onset in nonlacunar stroke.
In light of the generally negative data, the results of this trial may need to be
replicated.

22. Do antithrombotic agents reduce early stroke recurrence?
Platelet antiaggregants
CAST study (Class I).
Aspirin lowered the risk of recurrent ischemic stroke from 2.1 to 1.6%,
The risk of all recurrent strokes (hemorrhagic or ischemic) was not significantly
reduced.
CAST (Chinese Acute Stroke Trial) Collaboration Group. CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997;349:1641–1649.
IST study
Aspirin significantly reduced the rate of recurrent ischemic stroke from 3.9 to 2.8%.
Aspirin also reduced the combined rate of ischemic and hemorrhagic stroke from 4.7 to 3.7%.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneousheparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.

23. Overall, for aspirin there is a slight but statistically significant benefit in reducing recurrent stroke.

24. Unfractionated heparin
In randomized study (Class I).
Patients with: carotid-distribution, partial stable stroke
IV heparin did not prevent stroke progression within 7 days
(9/112 [17%] heparin vs 22/113 [19.5%] placebo)
There is no evidence that IV heparin reduces the risk of early recurrent stroke.
Duke RJ, Bloch FG, Turpie AGG, et al. Intravenous heparin for the prevention of stroke progression in acute partial stable stroke: a randomized
controlled trial. Ann Intern Med 1986;105:825–828.
IST study
SQ heparin -reduced the rate of recurrent ischemic stroke from 3.8 to 2.9%.
Benefit was balanced by an increased frequency of hemorrhagic stroke in the
heparin group (heparin-1.3% vs non-heparin, 0.4%).
Pretreatment CT scan was not required and, therefore, some hemorrhages may have been classified as ischemic stroke.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.

25. Low molecular weight heparins/heparinoids.
Study of 449 patients, (Class I).
LMW heparin (Dalteparin) VS Aspirin
Did not prevent early stroke progression (dalteparin- 10.7% vs aspirin- 7.6%; p=0.26)
Atrial fibrillation patients stroke recurrence (dalteparin-8.5% vs aspirin- 7.5%; p=0.26)
Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group Heparin in Acute Embolic Stroke Trial. Lancet 2000;355:1205–1210.
TOAST study (Class I)
Treated with Danaparoid
No statistical significance reduction in recurrent stroke.
Publications Committee for the Trial of ORG in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG (Dsanaparoid), and outcome after acute ischemic stroke. JAMA 1998;279:1265–1272.
Nadroparin was associated with a non-significant reduction in early stroke recurrence (3 patients on Nadroparin compared with 1 on placebo at 6 months).
Kay R, Sing Wong K, Yu YL, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995;333:1588–1593.

26. In 48 hours of onset of acute ischemic stroke
Heparin,LMW, heparinoids
Have not been shown to
reduce the rate of stroke recurrence.

27. Do antithrombotic agents vary in efficacy by stroke subtype?
Platelet antiaggregants.
CAST & IST studies
Used Oxfordshire Classification of ischemic stroke subtypes:
4 categories: total anterior circulation infarction, partial anterior circulation infarction, posterior infarction, lacunar infarction.
Aspirin did not reduce death or nonfatal stroke.
CAST (Chinese Acute Stroke Trial) Collaboration Group. CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997;349:1641–1649.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.

28. Heparin
Patients with atrial fibrillation do benefit from long-term anticoagulation for secondary stroke prevention
EAFT Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993;342:1255–1262.
limited data addressing the optimal time for beginning anticoagulation after an acute ischemic stroke.
IST trial -SQ heparin reduced acute recurrent cardioembolic stroke,
but increased ICH rate to a similar degree.
However, the level of anticoagulation was not measured during follow-up.
The study did not address the use of IV, dose-adjusted heparin

29. A randomized multi-centered study of immediate versus delayed anticoagulation of patients with cardio-embolic stroke
Immediate heparinization or no anticoagulants for the initial 14 days following stroke.
24 were immediately heparinized group – (Within 48 hours of onset )
in all sizes of embolic infarction
No major complications
0% recurrent stroke -
Control group
21 received no immediate anticoagulation.
2 –(10%) patients experienced early recurrent embolism.
2 hemorrhagic infarctions occurred in large infarcts.
A trend toward reduction of early recurrent embolism was apparent.
Efficacy of heparin in preventing early stroke recurrence

30. This supports immediate anticoagulation of non-hypertensive patients with embolic brain infarction who have no evidence of hemorrhage on CT performed hours after stroke.

31. “Stroke in progression” a potential indication for anticoagulation.
Difficulty in studying this condition :
Variability in its definition
Different time frames.
Patient with stroke may worsen from conditions not directly related.
The double-blind, placebo-controlled trial-
IV heparin to prevent stroke progression of noncardioembolic stroke
Continuous IV heparin within 48 hours of symptoms for 7 days (n=112) vs
Placebo (n=113).
No significant difference in stroke impairment and progression
Patients with progressing stroke and those with threatened basilar artery occlusion were specifically excluded from
the study.
Low rate of progression in the placebo patients limited the ability of the study to detect meaningful effect of
heparin
Worsening attributable to cerebral hemorrhage or hemorrhagic transformation did not occur in any patient.
Duke RJ, Bloch FG, Turpie AGG, et al. Intravenous heparin for the prevention of stroke progression in acute partial stable stroke: a randomized controlled trial. Ann Intern Med 1986;105:825–828.

32. Low molecular weight heparins/heparinoids
Analysis of TOAST data
Potential beneficial effect of Heparinoid, (Danaparoid)- was suggested in the subgroup of large artery atherosclerosis.
No efficacy was detected in cardioembolic and lacunar subgroups.
Publications Committee for the Trial of ORG in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG (Dsanaparoid), and outcome after acute ischemic stroke.JAMA 1998;279:1265–1272.
HAEST Study -Heparin in Acute Embolic Stroke Trial
LMW heparin was not more effective than aspirin in patients
with cardioembolic stroke caused by atrial fibrillation (Class I).
Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group Heparin in Acute Embolic Stroke Trial. Lancet 2000;355:1205–1210.

33. The slight, beneficial effect of aspirin in acute ischemic stroke not to be influenced by stroke subtype.
There is no convincing evidence that anticoagulants
are effective for any particular stroke subtype.
Danaparoid was of possible benefit in patients with a
large artery stroke
observation awaits prospective validation

34. Do antithrombotic agents reduce systemic thrombotic complications such as deep vein thrombosis and pulmonary emboli?
Pulmonary Emboli
Detected in 1% of stroke patients
Accounts for 10% of deaths after stroke,
Slows recovery & rehabilitation after stroke

35. SQ heparin Reduces the risk of PE and DVT.
In IST study- Pt on 12,500 IU SQ heparin
fewer PE within 14 days VS aspirin
(0.5% vs 0.8%; p=0.02)
5000 IU SQ heparin was not more
effective than aspirin in preventing PE.
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.

36. Low molecular weight heparins/heparinoids
TOAST – study
DVT :
(0.3%) on Danaparoid
(1.6%) on placebo (p <0.05)
PE : no significant reduction
(0.6) on placebo.
Publications Committee for the Trial of ORG in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG (Dsanaparoid), and outcome after acute ischemic stroke.
JAMA 1998;279:1265–1272.

37. Fraxiparine Ischemic Stroke Study (FISS)study
14 days of Nadroparin vs placebo
Reduction of PE from 5.6% to 1.7%.
Risk of symptomatic intracranial hemorrhage was not clearly increased.
Hommel M, for the FISS bis Investigators Group. Fraxiparine in ischaemic stroke study (FISS bis). Cerebrovasc Dis 1998; 8: 19.

38. LMWH may have a better benefit–risk profile than UFH.
Aspirin and mechanical prophylaxis are insufficient to prevent VTE in stroke patients.
Low dose prophylaxis of UFH and LMWH is associated with a low risk of ICH.
LMWH may have a better benefit–risk profile than UFH.
The optimal duration of prophylaxis is uncertain- extended prophylaxis in
immobilized patients may be beneficial.
Prevention of venous thromboembolism after acute ischemic Stroke : Ageno W, et al. Thromb Res Nov;124(5):e26-31

39. What are the risks of hemorrhage associated with antithrombotic agents?
5% of embolic stroke patients will have Sx ICH
In large infarcts, ICH may reach 20%, exceeding the risk of early recurrent embolism (about 12%).
In large infarcts- with risk for delayed hemorrhagic transformation, postponing anticoagulation for 5-7 days may be prudent.

40. Retrospectively collected 30 patients with cardiogenic embolic stroke and Hemorrhagic Transformation or ICH
- Analyzed risk factors
Severe Sx Hge Infarct and ICH largely confined to:
Anticoagulated patients with large infarcts.
In non-anticoagulated patients He Infarct is not rare, but commonly A-Sx

41. CAST & IST- aspirin increases the risk of systemic and CNS hemorrhage.
Platelet antiaggregants
CAST & IST- aspirin increases the risk of systemic and CNS hemorrhage.
CAST study -(Class I) % with aspirin
0.6% in non aspirin-treated (p=0.02)
CAST (Chinese Acute Stroke Trial) Collaboration Group. CAST: randomized placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997;349:1641–1649.
IST study -(Class II) % with aspirin treated
0.6% in non aspirin-treated (p=0.0004)
International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomized trial of aspirin, subcutaneous heparin, both, or neither among 19,435 patients with acute ischaemic stroke. Lancet 1997;349:1569 –1581.
Abciximab trial- no symptomatic major ICH through day 5 or to 3 months
The Abciximab in Ischemic Stroke Investigators. Abciximab in acute ischemic stroke: a randomized, double-blind, placebo-controlled, doseescalation study. Stroke 2000;31:601–609.
Multicenter Acute Stroke Trial– Italy:
Symptomatic ICH - aspirin-alone group - (7%)
similar or lower than no drug.
Multicentre Acute Stroke Trial–Italy (MAST-I) Group. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet 1995;346:1509–1514.

42. IST study SQ heparin (5000 U BID or 12,500 IU BID)
Increased risk of systemic & ICH
SQ heparin 1.2%
Control 0.4% (p< )
1.3% fatal or major systemic hemorrhage vs 0.4% for control
(p < ).

43. Low molecular weight heparins/heparinoids.
In TOAST, (Class I)
Serious systemic hemorrhage –
5.3% Danaparoid
2.7% of control.
Serious ICH
2.2% of Danaparoid
1.1% of control
Publications Committee for the Trial of ORG in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG (Dsanaparoid), and outcome after acute ischemic stroke. JAMA 1998;279:1265–1272.

44. Heparin in Acute Embolic Stroke Trial (Class I).
No difference in ICH between aspirin and Dalteparin.
Systemic hemorrhage higher in LMW heparin (5.8%) than aspirin group (1.8%)
Berge E, Abdelnoor M, Nakstad PH, Sandset PM. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study GroupHeparin in Acute Embolic Stroke Trial. Lancet 2000;355:1205–1210.
A (Class I) study in Hong Kong
systemic and hemorrhagic transformations were rare and not significantly different in Nadroparin [4.9%] vs placebo[8.6%]
Kay R, Sing Wong K, Yu YL, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995;333:1588–1593.
In TOPAS, (Class II).
Certoparin a parenchymal hemorrhage -2.2% .
More intracranial and extracranial bleeding in highest dose of Certoparin
Diener HC, Ringelstein EB, von Kummer R, et al. Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin. Results of the TOPAS Trial. Stroke 2001;32:22–29.

45. LMW heparin / heparinoids
Increased risk- both systemic and ICH
in patients treated with:
Aspirin
SQ heparin
LMW heparin / heparinoids

46. Recommendations
Patients within hours of stroke onset should be given aspirin (325 mg/day) to reduce stroke mortality and decrease morbidity (Grade A).
SQ heparin, LMW heparins, and heparinoids may be considered for DVT prophylaxis acute ischemic stroke, (Grade A).
SQ heparin -is not recommended for decreasing the risk of death, morbidity or recurrence (Grade A).
The benefit in reducing early recurrent ischemic stroke, negated by an increase in hemorrhage.

47. Dose-adjusted, IV heparin is not recommended for reducing morbidity, mortality, or early recurrent stroke in patients with acute stroke (not efficacious)
may be associated with increased bleeding complications (Grade B).
High-dose LMW heparin/heparinoids have not been associated with either benefit or harm in reducing morbidity, mortality, or early recurrent stroke (Grade A).
IV heparin or high-dose LMW heparin/heparinoids are not recommended for any specific subgroup of patients with acute ischemic stroke that is based on any presumed stroke mechanism or location (e.g., cardioembolic, large vessel atherosclerotic, vertebrobasilar, or “progressing” stroke)
insufficient data (Grade U).
Although the LMW heparin, dalteparin, at high doses may be efficacious
in patients with atrial fibrillation, it is not more efficacious than aspirin in this setting.
Because aspirin is easier to administer, it, rather than dalteparin, is recommended for the various stroke subgroups (Grade A).

48. IV heparin
Urgent anticoagulation is not recommended for acute ischemic stroke
(Class III, Level of Evidence A).
This may change if additional data demonstrate the usefulness of very early Tx of to large-artery thrombosis or cardioembolism.
Urgent anticoagulation is not recommended for patients
with moderate to severe strokes because of an increased risk of serious ICH (Class III, Level of Evidence A).
Initiation of anticoagulant therapy within 24 hours of IV rtPA is not recommended (Class III, Level of Evidence B).
(Stroke. 2007;38: )