Anticoagulant in Ischemic Stroke : An Evidence based medicine approach

Anticoagulant in Ischemic Anticoagulant in Ischemic Stroke : An Evidence Stroke : An Evidence

based medicine approachbased medicine approach

DefinitionsDefinitionsClass I Conditions for which there is evidence for and/or Class I Conditions for which there is evidence for and/or general agreement that the procedure or treatment is general agreement that the procedure or treatment is useful and effectiveuseful and effective

Class II Conditions for which there is conflicting evidence Class II Conditions for which there is conflicting evidence and/or a divergence of opinion about the and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatmentusefulness/efficacy of a procedure or treatment

Class IIa Weight of evidence or opinion is in favor of the Class IIa Weight of evidence or opinion is in favor of the procedure or treatmentprocedure or treatment..Class IIb Usefulness/efficacy is less well established by Class IIb Usefulness/efficacy is less well established by evidence or opinionevidence or opinion

Class III Conditions for which there is evidence and/or Class III Conditions for which there is evidence and/or general agreement that the procedure or treatment is general agreement that the procedure or treatment is not useful/effective and in some cases may be harmfulnot useful/effective and in some cases may be harmful

DefinitionsDefinitionsLevel of Evidence A: Data derived Level of Evidence A: Data derived from multiple randomized clinical from multiple randomized clinical trialstrials

Level of Evidence B: Data derived Level of Evidence B: Data derived from a single randomized trial or from a single randomized trial or nonrandomized studiesnonrandomized studies

Level of Evidence C: Expert opinion Level of Evidence C: Expert opinion or case studiesor case studies

recent definitionrecent definition

Stroke: either symptoms lasting 24 hours or Stroke: either symptoms lasting 24 hours or imaging of an acute clinically relevant brain imaging of an acute clinically relevant brain lesion in patients with rapidly vanishing lesion in patients with rapidly vanishing symptomssymptoms . .

•TIA :brief episode of neurological TIA :brief episode of neurological dysfunction caused by a focal disturbance of dysfunction caused by a focal disturbance of brain or retinal ischemia with clinical brain or retinal ischemia with clinical symptoms typically lasting less than 1 hour, symptoms typically lasting less than 1 hour, and without evidence of infarctionand without evidence of infarction”.”.

Stroke subtypesStroke subtypes

The use of anti-thrombotic agents is complicated by the existence of different stroke etiologic subtypes, each of which imparts a differential risk of

outcomes.In the early hours of presentation with an acutestroke, the mechanism of the infarction is frequentlynot clear and decisions regarding therapy are basedon presumptive diagnostic subtypes.

Stroke subtypes: large Stroke subtypes: large artery diseaseartery disease

Strokes caused by extracranial or intracranial large artery atherosclerosis appear to have the greatest risk of worsening and recurrence in the early period after hospitalization

American College of Chest Physicians Evidence-

Based Clinical Practice Guidelines (8th Edition). CHEST 2008; 133:630S-669S


In the NINDS Stroke Data Bank,

the atherosclerotic stroke subgroup had a 30% risk of worsening during the acute hospitalization and a 7.9% risk of stroke recurrence within 30 days.

Sacco RL et al. Stroke 1989; 20:983-989


In the North American Symptomatic Carotid Endarterectomy Trial (NASCET), medically treated patientswith transient ischemic attack (TIA) or stroke and ipsilateral carotid stenosis > 70% had a 26% risk of ipsilateral stroke at 2 years.

N Engl J Med 1991; 325:445-453


Causes of worsening and recurrence in patients with large artery atherosclerotic stroke include propagation or progression of the thrombosis, distal embolism, or failure of collateral vessels to compensatefor the reduced cerebral perfusion.

Stroke subtypes: embolic Stroke subtypes: embolic strokestroke

•one study found a high rate of early recurrence in a large group of cardioembolic stroke patients who had rheumatic heart disease, prosthetic valves, or documented intracardiac thrombi, but a sigdicantly lower recurrence rate in atrial fibrillation patients.

Berge E et al. Lancet 2000; 355:120Fj-1210Arch Intern Med 1994; 154:1449 -1457

Stroke subtypes: lacunar Stroke subtypes: lacunar infarctinfarct

Infarcts caused by small artery occlusions (lacunar strokes) have the lowestearly recurrence risk and the best survival rates, but still cause significant functional morbidity.

Stroke subtypes: Stroke subtypes: cryptogenic strokecryptogenic stroke

Some strokes are difficult to reliably classify into these categories and have been labeled cyptogenic infarcts.

Noninvasive vascular imaging fails to demonstrate an underlying large vessel occlusion or stenosis. No cardiac source of embolism is uncovered by echocardiography,ECG, or Holter monitoring

Anticoagulants for Anticoagulants for acute non-cardioembolic acute non-cardioembolic

StrokeStrokeStudies performed in the 1950s and 1960s suggested that IV heparin therapy may be beneficial for patients with unstable ischemic stroke with as much as a 50%reduction in the likelihood of further worsening .

These studies, however, were either not randomized orblinded, had poorly defined inclusion and exclusioncriteria, or did not use standardized assessments foroutcomes.

Sage JI.. Arch Neurol l9&5; 42:315-317


StrokeStrokeDespite the clinical use of full-dose IV unfractured heparin, to our knowledge, only a single randomized trial had evaluated this regimen compared with placebo for patients with acute stable stroke since 1980. No significant difference in stroke progression or neurologic outcome was detected in this relatively small study (n = 225).lo3T his trial had a broad treatment window of 48 h from stroke onset and excluded patients with progressing stroke.

Duke RJ et al. Ann Intern Med 1986; 105:825-828


StrokeStrokeA large metaanalysis of 22 trials among 23,547 patients showed that immediate anticoagulation of patients with acute ischemic stroke was not associated with a significant reduction in death or dependency.

Cochrane Database Syst Rev 2004. CD000024


StrokeStroke

For patients with acute ischemic For patients with acute ischemic stroke, we recommend stroke, we recommend againstagainst full- full-dose anticoagulation with IV, SC, or dose anticoagulation with IV, SC, or low-molecular-weight heparinslow-molecular-weight heparinsor heparinoids (Grade 1B)or heparinoids (Grade 1B)

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). CHEST 2008; 133:630S-

669S


StrokeStroke Urgent anticoagulation with the goal of

preventing early recurrent stroke, halting neurological worsening or improving outcomes after acute ischemic stroke is not recommended for treatment of patients with acute ischemic stroke (Class III, Level of Evidence A).

Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke AssociationCirculation 2007;115;e478-e534

Urgent anticoagulation is not recommended for patients with moderate to severe strokes because of an increased risk of serious intracranial hemorrhagic complications (Class III, Level of Evidence A).


Antiaggregants for Antiaggregants for acute non-cardioembolic acute non-cardioembolic

StrokeStroke

For patients with acute ischemic strokeFor patients with acute ischemic strokewho are not receiving thrombolysis, we who are not receiving thrombolysis, we recommend early aspirin therapy recommend early aspirin therapy (initial dose of 150-325 mg) [Grade lA](initial dose of 150-325 mg) [Grade lA]..


669S

Prevention of Prevention of Noncardioembolic Noncardioembolic

Cerebral Ischemic EventsCerebral Ischemic Events

For patients with noncardioembolicFor patients with noncardioembolicstroke or TIA, we recommend stroke or TIA, we recommend antiplateletantiplateletagents over oral anticoagulation agents over oral anticoagulation (Grade 1A)(Grade 1A)..

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). CHEST 2008; 133:630S-669S

(Class III, Level of Evidence C.)

The administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke


recent acute myocardial recent acute myocardial infarction, other acute infarction, other acute

coronary syndromecoronary syndrome•In those with a recent acute In those with a recent acute

myocardial infarction, other acute myocardial infarction, other acute coronary syndrome, or a recently coronary syndrome, or a recently placed coronary stent, we placed coronary stent, we recommend clopidogrel plus recommend clopidogrel plus aspirin aspirin ((75 to 100 mg75 to 100 mg)) [ [Grade 1AGrade 1A]. ]. The optimal duration of dual The optimal duration of dual antiplatelet therapy depends on antiplatelet therapy depends on the specific cardiac indicationsthe specific cardiac indications

atrial fibrillationatrial fibrillation

•In patients with atrial In patients with atrial fibrillation who have suffered a fibrillation who have suffered a recent stroke or TIA, we recent stroke or TIA, we recommend longrecommend long--term oral term oral anticoagulation anticoagulation ((target INR, target INR, 2.5; range, 2.0 to 3.02.5; range, 2.0 to 3.0)) [ [Grade Grade 1A1A]]..

atrial fibrillationatrial fibrillation

•we recommend initiation of oral we recommend initiation of oral anticoagulation therapy within 2 anticoagulation therapy within 2 weeks of a cardioembolic stroke; weeks of a cardioembolic stroke; however, for patients with large however, for patients with large infarcts or other risk factors for infarcts or other risk factors for hemorrhage, additional delays hemorrhage, additional delays may be appropriatemay be appropriate . .

aortic atherosclerotic aortic atherosclerotic lesionslesions

•In patients with stroke In patients with stroke associated with, we associated with, we recommend antiplatelet recommend antiplatelet therapy over no therapytherapy over no therapy ((Grade Grade 1A1A)) . .

mobile aortic arch thrombimobile aortic arch thrombi

•For patients with cryptogenic For patients with cryptogenic stroke associated with mobile stroke associated with mobile aortic arch thrombi, we aortic arch thrombi, we suggest either oral suggest either oral anticoagulation or antiplatelet anticoagulation or antiplatelet agentsagents ((Grade 2CGrade 2C))..

cryptogenic ischemic stroke cryptogenic ischemic stroke and a PFOand a PFO

•In patients with cryptogenic In patients with cryptogenic ischemic stroke and a PFO, we ischemic stroke and a PFO, we recommend antiplatelet recommend antiplatelet therapy over no therapytherapy over no therapy ((Grade Grade 1A1A) ) and suggest antiplatelet and suggest antiplatelet therapy over warfarintherapy over warfarin ((Grade Grade 2A2A)) . .

mitral valve strands or mitral valve strands or prolapseprolapse

• In patients with mitral valve In patients with mitral valve strands or prolapse who have a strands or prolapse who have a history of TIA or stroke, we history of TIA or stroke, we recommend antiplatelet recommend antiplatelet therapytherapy (Grade 1A) (Grade 1A)..

Embolic Stroke: Atrial Embolic Stroke: Atrial fibrillation(AF)fibrillation(AF)

•For patients with ischemic stroke For patients with ischemic stroke or TIA with persistent or or TIA with persistent or paroxysmal (intermittent) AF, paroxysmal (intermittent) AF, anticoagulation with adjusted-anticoagulation with adjusted-dose warfarin (target INR, 2.5; dose warfarin (target INR, 2.5; range, 2.0 to 3.0) is recommended range, 2.0 to 3.0) is recommended (Class I, Level of Evidence A)(Class I, Level of Evidence A)

Guidelines for Prevention of Stroke in Patients With Ischemic Stroke orTransient Ischemic Attack. Circulation. 2006;113;e409-e449

Embolic Stroke: Atrial Embolic Stroke: Atrial fibrillation(AF)fibrillation(AF)

For patients unable to take oral For patients unable to take oral anticoagulants, aspirin 325 mg/d is anticoagulants, aspirin 325 mg/d is recommended (Class I, Level ofrecommended (Class I, Level of Evidence A)Evidence A)..


.…75-325 mg/d (Grade 1B).


Embolic Stroke: recent Embolic Stroke: recent Myocardial infarctionMyocardial infarction

For patients with an ischemic stroke or For patients with an ischemic stroke or TIA caused by an acute MI in whom LV TIA caused by an acute MI in whom LV mural thrombus is identified by mural thrombus is identified by echocardiography or another form ofechocardiography or another form of cardiac imaging, oral anticoagulation cardiac imaging, oral anticoagulation is reasonable, aiming for an INR of 2.0 is reasonable, aiming for an INR of 2.0 to 3.0 for at least 3 months and up to to 3.0 for at least 3 months and up to 1 year (Class IIa, Level of Evidence B)1 year (Class IIa, Level of Evidence B)..


Embolic Stroke: recent Embolic Stroke: recent Myocardial infarctionMyocardial infarction

•Aspirin should be used Aspirin should be used concurrently for ischemic concurrently for ischemic coronary artery disease during coronary artery disease during oral anticoagulant therapy in oral anticoagulant therapy in doses up to 162 mg/d (Class doses up to 162 mg/d (Class IIa, Level of Evidence A)IIa, Level of Evidence A)..


Embolic Stroke: dilated Embolic Stroke: dilated cardiomyipathycardiomyipathy

For patients with ischemic stroke or For patients with ischemic stroke or TIA who have dilated TIA who have dilated cardiomyopathy, either warfarin cardiomyopathy, either warfarin (INR, 2.0 to 3.0) or antiplatelet (INR, 2.0 to 3.0) or antiplatelet therapy may be considered for therapy may be considered for prevention of recurrent events prevention of recurrent events (Class IIb, Level of Evidence C)(Class IIb, Level of Evidence C)


Embolic Stroke: mitral Embolic Stroke: mitral valve diseasevalve disease

For patients with ischemic stroke For patients with ischemic stroke or TIA who have rheumatic or TIA who have rheumatic mitral valve disease, whether or mitral valve disease, whether or not AF is present, long-term not AF is present, long-term warfarin therapy is reasonable, warfarin therapy is reasonable, with a target INR of 2.5 (range, with a target INR of 2.5 (range, 2.0 to 3.0) (Class IIa, Level of 2.0 to 3.0) (Class IIa, Level of Evidence C)Evidence C) . .



Antiplatelet agents should Antiplatelet agents should notnot routinely be added to warfarin to routinely be added to warfarin to avoid the additional bleeding risk avoid the additional bleeding risk (Class III, Level of Evidence C)(Class III, Level of Evidence C)..



•For patients with ischemic stroke or For patients with ischemic stroke or TIA with rheumatic mitral valve TIA with rheumatic mitral valve disease, whether or not AF is present, disease, whether or not AF is present, who have a recurrent embolism while who have a recurrent embolism while receiving warfarin, adding aspirin (81 receiving warfarin, adding aspirin (81 mg/d) is suggested (Class IIa, Level of mg/d) is suggested (Class IIa, Level of Evidence C)Evidence C)

•Guidelines for Prevention of Stroke in Patients With Ischemic Stroke orTransient Ischemic Attack. Circulation. 2006;113;e409-e449

Embolic Stroke: mitral Embolic Stroke: mitral valve prolapsevalve prolapse

For patients with mitral valve For patients with mitral valve prolapse who have ischemic prolapse who have ischemic stroke or TIAs, antiplatelet stroke or TIAs, antiplatelet therapy is reasonable (ClassIIa, therapy is reasonable (ClassIIa, Level of Evidence C)Level of Evidence C) Guidelines for Prevention of Stroke in Patients With Ischemic Stroke orTransient Ischemic Attack. Circulation. 2006;113;e409-e449

..…..…Grade I AGrade I AAmerican College of Chest Physicians Evidence-


Embolic Stroke: Mitral Embolic Stroke: Mitral Annular Annular

Calcification(MAC)Calcification(MAC) •For patients with ischemic stroke For patients with ischemic stroke

or TIA and Mitral Annular or TIA and Mitral Annular Calcification(MAC) not Calcification(MAC) not documented to be calcific, documented to be calcific, antiplatelet therapy may be antiplatelet therapy may be considered (Class IIb, Level of considered (Class IIb, Level of Evidence C)Evidence C)..


Embolic Stroke: Mitral Embolic Stroke: Mitral Annular Annular

Calcification(MAC)Calcification(MAC)•Among patients with mitral Among patients with mitral

regurgitation caused by MAC regurgitation caused by MAC without AF, antiplatelet or without AF, antiplatelet or warfarin therapy may be warfarin therapy may be considered (Class IIb, Level of considered (Class IIb, Level of Evidence C)Evidence C)


Embolic Stroke: aortic Embolic Stroke: aortic valve diseasevalve disease

•For patients with ischemic For patients with ischemic stroke or TIA and who do not stroke or TIA and who do not have AF, antiplatelet therapy have AF, antiplatelet therapy may be considered (Class IIb, may be considered (Class IIb, Level of Evidence C)Level of Evidence C)


Embolic Stroke: Embolic Stroke: prosthetic heart valvesprosthetic heart valves

•For patients with ischemic stroke or For patients with ischemic stroke or TIA who have modern mechanical TIA who have modern mechanical prosthetic heart valves, oral prosthetic heart valves, oral anticoagulants are recommended, anticoagulants are recommended, with an INR target of 3.0 (range, 2.5 with an INR target of 3.0 (range, 2.5 to 3.5) (Class I, Level ofEvidence B)to 3.5) (Class I, Level ofEvidence B)..



For patients with mechanical prosthetic For patients with mechanical prosthetic heart valves who have an ischemic heart valves who have an ischemic stroke or systemic embolism despite stroke or systemic embolism despite adequate therapy with oral adequate therapy with oral anticoagulants, aspirin 75 to 100 mg/d anticoagulants, aspirin 75 to 100 mg/d in addition to oral anticoagulants and in addition to oral anticoagulants and maintenance of the INR at a target of maintenance of the INR at a target of 3.0(range 2.5 to 3.5) are reasonable 3.0(range 2.5 to 3.5) are reasonable (Class IIa, Level of Evidence B)(Class IIa, Level of Evidence B)..



•For patients with ischemic stroke For patients with ischemic stroke or TIA who have bioprosthetic heart or TIA who have bioprosthetic heart valves with no other source of valves with no other source of thromboembolism, anticoagulation thromboembolism, anticoagulation with warfarin (INR 2.0 to 3.0) may with warfarin (INR 2.0 to 3.0) may be considered (Class IIb, Levelof be considered (Class IIb, Levelof Evidence C)Evidence C)..


Embolic stroke: patent foramen ovale

In patients with cryptogenic ischemicIn patients with cryptogenic ischemicstroke and a patent foramen ovale, we stroke and a patent foramen ovale, we recomrecom--mend antiplatelet therapy over no therapymend antiplatelet therapy over no therapy

((Grade 1AGrade 1A ) )and suggest antiplatelet agentsand suggest antiplatelet agentsover anticoagulation (Grade 2A)over anticoagulation (Grade 2A)..


Embolic stroke: aortic Embolic stroke: aortic plaqueplaque

In patients with stroke In patients with stroke associated with aorassociated with aortic tic atherosclerotic lesions, we atherosclerotic lesions, we recommend anti-platelet recommend anti-platelet therapy over no therapy therapy over no therapy (Grade 1A)(Grade 1A) . .

American College of Chest Physicians GvidencBased Clinical Practice Guidelines (8th Edition). CHEST 2008;

133:630S-669S

Embolic stroke: aortic Embolic stroke: aortic plaqueplaque

For patients with cryptogenic For patients with cryptogenic stroke associated with mobile stroke associated with mobile aortic arch thrombi, we aortic arch thrombi, we suggest either oral suggest either oral anticoagulation or antiplatelet anticoagulation or antiplatelet agents (Grade 2C)agents (Grade 2C)..

American College of Chest Physicians GvidencBased Clinical Practice Guidelines (8th Edition).

CHEST 2008; 133:630S-669S

venous sinus thrombosisvenous sinus thrombosis

• we recommend that clinicians use we recommend that clinicians use UFHUFH ((Grade 1BGrade 1B) ) or lowor low--molecularmolecular--weight heparinweight heparin ((Grade 1BGrade 1B) ) over no over no anticoagulant therapy during the anticoagulant therapy during the acute phase, even in the presence of acute phase, even in the presence of hemorrhagic infarctionhemorrhagic infarction. . In these In these patients, we recommend continued patients, we recommend continued use of vitamin K antagonist therapy use of vitamin K antagonist therapy for up to 12 months for up to 12 months ((target INR, 2.5; target INR, 2.5; range, 2.0–3.0range, 2.0–3.0)) [ [Grade 1BGrade 1B]] . .

neuroprotective actions

At present, no intervention with putative neuroprotective actions has been established as effective in improving outcomes after stroke, and therefore none currently can be recommended (Class III, Level of Evidence A).


osmotherapy

Although aggressive medical measures, including osmotherapy, have been recommended for treatment of deteriorating patients with malignant brain edema after large cerebral infarction, these measures are unproven (Class IIa, Level of Evidence C). Hyperventilation is a short-lived intervention. Medical measures may delay decompressive surgeryGuidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke AssociationCirculation 2007;115;e478-e534

anticonvulsants

Prophylactic administration of anticonvulsants to patients with stroke but who have not had seizures is not recommended (Class III, Level of Evidence C) .


Prevention of DeepPrevention of DeepVein Thrombosis and Vein Thrombosis and Pulmonary EmbolismPulmonary Embolism

For acute stroke patients with restrictedFor acute stroke patients with restrictedmobility, we recommend prophylactic mobility, we recommend prophylactic low-dose SC heparin or low-molecular-low-dose SC heparin or low-molecular-weight heparins (Grade IA)weight heparins (Grade IA)..


669S


For patients who have contraindcations For patients who have contraindcations to anticoagulants, we recommend to anticoagulants, we recommend intennittent pneumatic compression intennittent pneumatic compression (IPC) devices or elastic (IPC) devices or elastic stockings(Grade 1B)stockings(Grade 1B)..


669S


In patients with an acute In patients with an acute intracerebralintracerebralhematoma (ICH), we recommend the hematoma (ICH), we recommend the initial use of IPC devices (Grade 1B)initial use of IPC devices (Grade 1B)..



•In stable patients with an acute In stable patients with an acute intracerebral hematoma (ICH),, we intracerebral hematoma (ICH),, we suggest low-dose SCheparin as suggest low-dose SCheparin as soon as the second day after the soon as the second day after the onset of the hemorrhage (Grade 2C)onset of the hemorrhage (Grade 2C)

American College of Chest Physicians GvidencBased Clinical Practice Guidelines (8th Edition). CHEST 2008; 133:630S-

669S

•For acute stroke patients with For acute stroke patients with restricted mobility, we restricted mobility, we recommend prophylactic lowrecommend prophylactic low--dose SC heparin or lowdose SC heparin or low--molecularmolecular--weight heparinsweight heparins ((Grade 1AGrade 1A))..

Thrombolytic TherapyThrombolytic Therapy

Inclusion CriteriaInclusion Criteria

•Age ≥18 yearsAge ≥18 years , ,•clinical diagnosis of stroke with a clinical diagnosis of stroke with a

clinically meaningful neurologic clinically meaningful neurologic deficitdeficit , ,

•clearly defined time of onset of <180 clearly defined time of onset of <180 min before treatmentmin before treatment , ,

• baseline CT showing no evidence of baseline CT showing no evidence of intracranial hemorrhageintracranial hemorrhage..

Exclusion CriteriaExclusion Criteria

•Minor or rapidly improving symptoms or signsMinor or rapidly improving symptoms or signs , ,•CT signs of intracranial hemorrhageCT signs of intracranial hemorrhage , ,

•a history of intracranial hemorrhage, seizure at a history of intracranial hemorrhage, seizure at stroke onset, stroke or serious head injury within stroke onset, stroke or serious head injury within 3 months3 months,,

• major surgery or serious trauma within 2 weeksmajor surgery or serious trauma within 2 weeks , ,•GI or urinary tract hemorrhage within 3 weeksGI or urinary tract hemorrhage within 3 weeks , ,•systolic BP >185 mm Hg, diastolic BP >110 mm systolic BP >185 mm Hg, diastolic BP >110 mm

Hg, aggressive treatment required to lower BPHg, aggressive treatment required to lower BP , ,•glucose <50 mg/dL or >400 mg/dLglucose <50 mg/dL or >400 mg/dL , ,

•symptoms of subarachnoid hemorrhagesymptoms of subarachnoid hemorrhage , ,•arterial puncture at a noncompressible site or arterial puncture at a noncompressible site or

lumbar puncture within 1 weeklumbar puncture within 1 week,,• platelet count <100,000/mm3platelet count <100,000/mm3,,

• heparin therapy within 48 h associated with heparin therapy within 48 h associated with elevated activated partial thromboplastin timeelevated activated partial thromboplastin time , ,

•clinical presentation suggesting post-clinical presentation suggesting post-myocardial infarction pericarditismyocardial infarction pericarditis,,

• pregnant womenpregnant women,,• anticoagulation due to oral anticoagulants anticoagulation due to oral anticoagulants

(international normalized ratio [INR] >1.7)(international normalized ratio [INR] >1.7)..

((Grade 1AGrade 1A.).)

•For eligible patients, we For eligible patients, we recommend administration of IV recommend administration of IV tPA in a dose of 0.9 mgtPA in a dose of 0.9 mg//kg kg ((maximum of 90 mgmaximum of 90 mg)), with 10% of , with 10% of the total dose given as an initial the total dose given as an initial bolus and the remainder infused bolus and the remainder infused over 60 min, provided that over 60 min, provided that treatment is initiated within 3 h treatment is initiated within 3 h of clearly defined symptom onsetof clearly defined symptom onset

((Grade 2BGrade 2B))

•For patients with extensive (more For patients with extensive (more than one third of the middle than one third of the middle cerebral artery territory) and cerebral artery territory) and clearly identifiable hypodensity clearly identifiable hypodensity on CT, we suggest not using of on CT, we suggest not using of tPAtPA



((Grade 2AGrade 2A))

•For patients with acute ischemic For patients with acute ischemic stroke of >3 h but <4.5 h we stroke of >3 h but <4.5 h we suggest clinicians do not use IV suggest clinicians do not use IV tPAtPA




•For patients with acute stroke For patients with acute stroke onset of >4.5 h, we recommend onset of >4.5 h, we recommend against the use of IV tPAagainst the use of IV tPA




• For patients with acute For patients with acute ischemic stroke, we recommend ischemic stroke, we recommend against streptokinaseagainst streptokinase



((Grade 2CGrade 2C))

•For patients with angiographically For patients with angiographically demonstrated middle cerebral artery demonstrated middle cerebral artery occlusion and without major early occlusion and without major early infarct signs on the baseline CT or MRI infarct signs on the baseline CT or MRI scan, who can be treated within 6 h of scan, who can be treated within 6 h of symptom onset, we suggest symptom onset, we suggest intraarterial thrombolytic therapy with intraarterial thrombolytic therapy with tPA for selected patients in centers tPA for selected patients in centers with the appropriate neurologic and with the appropriate neurologic and interventional expertiseinterventional expertise

((Grade 2CGrade 2C.).)

•For patients with acute basilar artery For patients with acute basilar artery thrombosis and without major CT/MRI thrombosis and without major CT/MRI evidence of infarction, we suggest evidence of infarction, we suggest either intraarterial or IV thrombolysis either intraarterial or IV thrombolysis with tPA depending on available with tPA depending on available resources and capabilitiesresources and capabilities



Documents

Anticoagulant in Ischemic Stroke : An Evidence based medicine approach