Ischemic stroke medical therapy: Difference between revisions

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===Reperfusion therapy===
For 2015 AHA/ASA guidelines on medical therapy of ischemic stroke, please click here.  
====Intravascular====
'''Within 3 hours'''<br>
'''3-4.5 hours'''<br>
'''> 4 hours'''
 
====Intraarterial====
'''Mechanical thrombectomy'''
 
An ischemic stroke is due to a [[thrombus]] (blood clot) occluding a cerebral artery, a patient is given [[antiplatelet drug|antiplatelet medication]] ([[aspirin]], [[clopidogrel]], [[dipyridamole]]), or [[anticoagulant]] medication ([[warfarin]]), dependent on the cause, when this type of stroke has been found. Hemorrhagic stroke must be ruled out with medical imaging, since this therapy would be harmful to patients with that type of stroke.
 
Whether thrombolysis is performed or not, the following investigations are required:
* Stroke symptoms are documented, often using scoring systems such as the National Institutes of Health Stroke Scale, the [[Cincinnati Stroke Scale]], and the Los Angeles Prehospital Stroke Screen. The Cincinnati Stroke Scale is used by [[emergency medical technician]]s (EMTs) to determine whether a patient needs transport to a stroke center.
* A [[Computed axial tomography|CT scan]] is performed to rule out hemorrhagic stroke
* Blood tests, such as a [[full blood count]], [[coagulation]] studies ([[prothrombin time|PT/INR]] and [[Partial thromboplastin time|APTT]]), and tests of [[electrolyte]]s, [[renal function]], [[liver function tests]] and [[glucose]] levels are carried out.
 
Other immediate strategies to protect the brain during stroke include ensuring that [[blood sugar]] is as normal as possible (such as commencement of an insulin sliding scale in known [[diabetes|diabetics]]), and that the stroke patient is receiving adequate [[oxygen]] and [[intravenous fluid]]s. The patient may be positioned so that his or her head is flat on the stretcher, rather than sitting up, since studies have shown that this increases blood flow to the brain. Additional therapies for ischemic stroke include [[aspirin]] (50 to 325 mg daily), [[clopidogrel]] (75 mg daily), and combined aspirin and [[dipyridamole]] extended release (25/200 mg twice daily).
 
It is common for the [[blood pressure]] to be [[arterial hypertension|elevated]] immediately following a stroke. Studies indicated that while high blood pressure causes stroke, it is actually beneficial in the emergency period to allow better blood flow to the brain.
 
If studies show [[carotid stenosis]], and the patient has residual function in the affected side, [[carotid endarterectomy]] (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after stroke.
 
If the stroke has been the result of [[cardiac arrhythmia]] with cardiogenic emboli, treatment of the arrhythmia and [[anticoagulation]] with [[warfarin]] or high-dose aspirin may decrease the risk of recurrence.  Stroke prevention treatment for a common arrhythmia, [[atrial fibrillation]], is determined according to the [[CHADS Score|CHADS/CHADS2 system]].
 
====Anticoagulant Recommendations Following Ischemic Stroke====
 
Currently, the European Stroke Organization recommends that anticoagulation should not be used after non-cardio-embolic ischemic stroke, except in some specific situations, such as aortic [[atheroma]]s, fusiform [[aneurysm]]s of the [[basilar artery]], cervical artery dissection, or [[patent foramen ovale]] in the presence of proven [[deep vein thrombosis]] ([[DVT]]) or atrial septal aneurysm. Data suggest that oral anticoagulation after non-cardiac ischemic stroke is ''not'' superior to [[aspirin]], but may be associated with more bleeding.
 
====Antiplatelet Recommendations Following Ischemic Stroke====
Although the combination of [[clopidogrel]] and [[aspirin]] is prescribed for patients with [[acute coronary syndromes]] ([[ACS]]), this combination has not been studied in the setting of acute ischemic stroke. No data are available about the use of other combinations of antiplatelet agents in the management of acute ischemic stroke. The current American Stroke Association (ASA) / American Heart Association (AHA) recommendations are the following:
 
:"The administration of clopidogrel alone or in combination with aspirin is not recommended for the treatment of acute ischemic stroke (Class III, Level of Evidence C)."
 
The 2008 American College of Chest Physician (ACCP) Guidelines, similar to the AHA/ASA Guidelines, state the following:
 
:4.1.3. "In most patients with a noncardioembolic stroke or [[transient ischemic attack]], were recommend avoiding long-term use of the combination of [[aspirin]] and [[clopidogrel]] (Grade1B).  In those with a recent [[acute myocardial infarction]], other [[acute coronary syndrome]], or a recently placed coronary stent, we recommend [[clopidogrel]] plus [[aspirin]] (75-100mg) [Grade1A]."
 
There is no data available regarding the safety and efficacy of dual antiplatelet therapy in addition to chronic anticoagulation for patients with non-cardio-embolic-ischemic stroke.  It should be noted that more potent platelet inhibition with [[prasugrel]] was associated with a higher risk of adverse outcomes compared to [[clopidogrel]] in the Triton study among patients who had sustained a prior stroke or [[transient ischemic attack]] ([[TIA]]).
 
====Thrombolysis====
In increasing numbers of primary stroke centers, pharmacologic [[thrombolysis]] ("clot busting") with the drug [[tissue plasminogen activator]], '''tPA''',  is used to dissolve the clot and unblock the artery. However, the use of tPA in acute stroke is controversial.  On one hand, it is endorsed by the [[American Heart Association]] and the American Academy of Neurology as the recommended treatment for acute stroke within three hours of onset of symptoms as long as there are not other contraindications (such as abnormal lab values, high blood pressure, or recent surgery).
 
This position for tPA is based upon the findings of two studies by one group of investigators<ref>{{cite journal |author= |title=Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group |journal=New England Journal of Medicine |volume=333 |issue=24 |pages=1581–7 |year=1995 |pmid=7477192 |url=http://content.nejm.org/cgi/content/full/333/24/1581}}</ref>  which showed that tPA improves the chances for a good neurological outcome. When administered within the first three hours, 39% of all patients who were treated with tPA had a good outcome at three months, only 26% of placebo controlled patients had a good functional outcome.  However, in the NINDS trial 6.4% of patients with large strokes developed substantial brain hemorrhage as a complication from being given tPA. tPA is often misconstrued as a "magic bullet" and it is important for patients to be aware that despite the study that supports its use, some of the data were flawed and the safety and efficacy of tPA is controversial. A recent study found the mortality to be higher among patients receiving tPA versus those who did not.<ref name="Dubinsky06">{{cite journal | last =Dubinsky  | first = R| authorlink = | coauthors =Lai SM | title =Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample | journal =Neurology | volume =66 | issue =11 | pages =1742–1744 | publisher = | date =2006 | url = | doi = | id =PMID 16769953  | accessdate =2007-01-22 }} </ref> Additionally, it is the position of the American Academy of Emergency Medicine that objective evidence regarding the efficacy, safety, and applicability of tPA for acute ischemic stroke is insufficient to warrant its classification as [[standard of care]].<ref>{{cite web|url=http://www.aaem.org/positionstatements/thrombolytictherapy.shtml |title=Position Statement on the Use of Intravenous Thrombolytic Therapy in the Treatment of Stroke |publisher=American Academy of Emergency Medicine |accessdate=2008-01-25}}</ref>  Until additional evidence clarifies such controversies, physicians are advised to use their discretion when considering its use. Given the cited absence of definitive evidence, AAEM believes it is inappropriate to claim that either use or non-use of intravenous thrombolytic therapy constitutes a standard of care issue in the treatment of stroke.
 
In 2014, a [[meta-analysis]] by the [[Cochrane Collaboration]] reported the following findings with the administration of recombinant [[tissue plasminogen activator]] (also known as [[alteplase]] or rt-PA) within 6 hours of the onset of stroke:<ref name="pmid25072528">{{cite journal| author=Wardlaw JM, Murray V, Berge E, del Zoppo GJ| title=Thrombolysis for acute ischaemic stroke. | journal=Cochrane Database Syst Rev | year= 2014 | volume= 7 | issue=  | pages= CD000213 | pmid=25072528 | doi=10.1002/14651858.CD000213.pub3 | pmc=PMC4153726 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25072528  }} </ref>
* Reduction in combined outcome of disability and death
* No increase in death
 
An individual patient [[meta-analysis]] by the Stroke Thrombolysis Trialists' Collaborative Group reported the following findings with the administration of recombinant [[tissue plasminogen activator]] (rt-PA):<ref name="pmid25106063">{{cite journal| author=Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E et al.| title=Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. | journal=Lancet | year= 2014 | volume=  | issue=  | pages=  | pmid=25106063 | doi=10.1016/S0140-6736(14)60584-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25106063  }} </ref>
* 10% absolute increase of a good outcome, defined as no significant disability at 3-6 months (modified Rankin Score of 0 or 1)
* 2% absolute increase risk of early death from [[intracranial hemorrhage]]
 
====Embolic Stroke====
Anticoagulation can prevent recurrent stroke. Among patients with nonvalvular  [[atrial fibrillation]], anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%.<ref name="pmid17577005">{{cite journal |author=Hart RG, Pearce LA, Aguilar MI |title=Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation |journal=Ann. Intern. Med. |volume=146 |issue=12 |pages=857-67 |year=2007 |pmid=17577005 |doi=}}</ref>. However, a recent  [[meta-analysis]] suggests harm from anti-coagulation started early after an embolic stroke.<ref name="pmid17204681"> {{cite journal  |author=Paciaroni M, Agnelli G, Micheli S, Caso V |title=Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials |journal=Stroke |volume=38  |issue=2 |pages=423-30 | year=2007 |pmid=17204681 |doi=10.1161/01.STR.0000254600.92975.1f }} [http://www.acpjc.org/Content/147/1/issue/ACPJC-2007-147-1-017.htm ACP JC synopsis ]</ref>
 
===Hemorrhagic Stroke===
[[Anticoagulant]]s and antithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage. Patients are monitored and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.
 
===Contraindicated Medications===
 
{{MedCondContrAbs
 
|MedCond = Stroke|Abciximab|Almotriptan|Alteplase|Conjugated estrogens/bazedoxifene|Drospirenone and Ethinyl estradiol|Eletriptan|Eptifibatide|Esterified estrogens|Frovatriptan|Medroxyprogesterone|Norethindrone acetate and Ethinyl estradiol|Norgestimate and Ethinyl estradiol|Norelgestromin and Ethinyl Estradiol|
|Phentermine|Prasugrel|Progesterone|Rizatriptan|Reteplase|Streptokinase|Urokinase|Vorapaxar|Norgestrel and Ethinyl estradiol|Sumatriptan|Zolmitriptan}}


==The 2007 American Heart Association (AHA) / American Stroke Association (ASA) Guidelines (DO NOT EDIT)==
==The 2007 American Heart Association (AHA) / American Stroke Association (ASA) Guidelines (DO NOT EDIT)==

Revision as of 22:29, 18 November 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

Overview

Treatment of stroke is occasionally with thrombolysis ("clot buster"), but usually with supportive care (physiotherapy and occupational therapy) and secondary prevention with antiplatelet drugs (aspirin and often dipyridamole), blood pressure control, statins and anticoagulation (in selected patients).[1]

Medical Therapy

Ischemic Stroke

Medical treatment Drug class Recommendations
Acute Long-Term
Reperfusion therapy Tissue plasminogen activator (t-PA)
  • Recommended within 3-4.5 hours of onset of ischemic stroke in eligible patients[2][3][4][5][6][7]
  • None
Antithrombotic agents Antiplatelet agents
  • Oral administration of aspirin (initial dose is 325 mg) is recommended within 24 to 48 hours after stroke onset in most patients[2]
  • Aspirin is contraindicated in patients with ischemic stroke within 24 hours of t-PA administration[2]
  • DAPT therapy (aspirin and clopidogrel) is recommended for 90 days in patients with symptomatic intracranial large artery disease
  • Long term therapy with clopidogrel or aspirin extended release dipyridamole may be used for secondary prevention of non cardioembolic stroke
Anticoagulants
  • Parenteral or oral anticoagulation is not recommended within 48 hours of onset of ischemic stroke[8]
  • Oral anticoagulants may be used for secondary prevention of ischemic stroke in patients with atrial fibrillation or other cardioembolic disease[9]
Antilipid therapy Statins
  • Among patients already taking statins at the time of onset of ischemic stroke, continuation of statin therapy during the acute period is reasonable[2]
  • Long term management of ischemic stroke with high intensity statins may be recommended for patients with atherosclerotic disease
  • Patients who cannot tolerate high intensity dose, medium or low intensity statins may prove beneficial
Antihypertensive therapy Intravenous antihypertensives

(Labetolol, nitroprusside)

  • Used to control high blood pressure in patients with BP>185/110 mmHg before starting t-PA[2]
  • Long term oral antihypertensives may be used after 24 hours of ischemic stroke in patients having history of hypertension
Oral antihypertensive therapy
  • Long term oral antihypertensives may be used after 24 hours of ischemic stroke in patients having history of hypertension
Antihyperglycemic agents Insulin
  • May be used to control blood glucose between range of 140-180 mg/dl since hyperglycemia is associated with worst outcome in patients with acute ischemic stroke[2]
  • Long term oral antidiabetic may be used for secondary prevention of ischmeic stroke in patients with diabetes mellitus

For 2015 AHA/ASA guidelines on medical therapy of ischemic stroke, please click here.

The 2007 American Heart Association (AHA) / American Stroke Association (ASA) Guidelines (DO NOT EDIT)

Class III (Harm)
"1.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 (Level of Evidence: A)This recommendation may change if additional data demonstrate the usefulness of very early intravenous administration of anticoagulants for treatment of patients with infarctions secondary to large-artery thrombosis or cardioembolism. Urgent anticoagulation should not be used in lieu of intravenous thrombolysis for treatment of otherwise eligible patients (Level of Evidence: A)"
"2.Urgent anticoagulation is not recommended for patients with moderate to severe strokes because of an increased risk of serious intracranial hemorrhagic complications (Level of Evidence: A)"
"3.Initiation of anticoagulant therapy within 24 hours of treatment with intravenously administered rtPA is not recommended (Level of Evidence: A)"

References

  1. Hackam DG, Spence JD (2007). "Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study". Stroke. 38 (6): 1881–5. doi:10.1161/STROKEAHA.106.475525. PMID 17431209.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Jauch EC, Saver JL, Adams HP, Bruno A, Connors JJ, Demaerschalk BM; et al. (2013). "Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association". Stroke. 44 (3): 870–947. doi:10.1161/STR.0b013e318284056a. PMID 23370205.
  3. "Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group". New England Journal of Medicine. 333 (24): 1581–7. 1995. PMID 7477192.
  4. Dubinsky, R (2006). "Mortality of stroke patients treated with thrombolysis: analysis of nationwide inpatient sample". Neurology. 66 (11): 1742–1744. PMID 16769953. Unknown parameter |coauthors= ignored (help); |access-date= requires |url= (help)
  5. "Position Statement on the Use of Intravenous Thrombolytic Therapy in the Treatment of Stroke". American Academy of Emergency Medicine. Retrieved 2008-01-25.
  6. Wardlaw JM, Murray V, Berge E, del Zoppo GJ (2014). "Thrombolysis for acute ischaemic stroke". Cochrane Database Syst Rev. 7: CD000213. doi:10.1002/14651858.CD000213.pub3. PMC 4153726. PMID 25072528.
  7. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E; et al. (2014). "Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials". Lancet. doi:10.1016/S0140-6736(14)60584-5. PMID 25106063.
  8. Paciaroni M, Agnelli G, Micheli S, Caso V (2007). "Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials". Stroke. 38 (2): 423–30. doi:10.1161/01.STR.0000254600.92975.1f. PMID 17204681. ACP JC synopsis
  9. Hart RG, Pearce LA, Aguilar MI (2007). "Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation". Ann. Intern. Med. 146 (12): 857–67. PMID 17577005.


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