current treatment of transient ischemic attack

CURRENT MANAGEMENT OFTRANSIENT ISCHEMIC ATTACK

Sen. Col.Assoc. Prof. Samart NidhinandanaDirector of department of Psychiatry and Neurology

Head of PMK Stroke CenterPhramongkutklao Hospital and College of Medicine

Friday, August 22, 2014

ชายไทยคู ่อายุ 78 ปีวันที ่6 กุมภาพันธ์ 06.20 น.มีอาการแขนขาด้านขวาอ่อนแรง มาถึง

รพ.เวลา 10.42 น.

สัญญาณชีพ ความดันเลือด 140/80 มม.ปรอท อัตราชีพจร 88 ครั้งต่อนาที อัตราการหายใจ 20 ครั้งต่อนาท ี

ตรวจร่างกาย ปกติ ไม่พบอาการอ่อนแรง

ตรวจระดับน้ําตาลในเลือดจากปลายนิ้วได้ 99 มก./ดล. ตรวจปัสสาวะปกติ แพทย์ให้คําวินิจฉัยว่า Transient Ischemic Attack

และให้คําแนะนํา นัดมาตรวจเลือดหาระดับน้ําตาล ไขมัน วันที ่11

กุมภาพันธ์ Friday, August 22, 2014

คําถาม

ท่านคิดว่าแพทย์ให้การวินิจฉัย และการรักษาถูกต้องหรือไม่ ?


คําจํากัดความTRANSIENT ISCHEMIC ATTACK

Transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.

Easton JD., Saver JL.,Albers GW et al.Stroke 2009;40:2276-2293.


ABCD2

score caseAge>60 1 1

BP>140 1 1

Clinical

Focal deficit 2 2

Dysarthria 1 0

Duration

>60 min 2 2

10-59 min 1 0

DM 1 0


STROKE RISK USING ABCD2 SCORE

Two-day risk of stroke in combined validation cohorts

No randomized trial has evaluated the utility of the ABCD2 score in assisting with triage decisions

ABCD2 SCORE STROKE RISK

0 - 1 0%

2 - 3 1.3%

4 - 5 4.1%

6 - 7 8.1%


Multicenter study of early stroke risk based on ABCD2 score and tissue-vs. time-defined TIA (n = 4574)

Giles MF et al., Neurology 2011;77:1222-1228


HOSPITALIZATION

Hospitalization rates after TIA vary widely among practitioners, hospitals, and regions

Close observation during hospitalization has the potential to allow more rapid and frequent administration of tPA should a stroke occur.

Other benefits: cardiac monitoring , rapid diagnostic evaluation, greater rates of adherence to secondary prevention interventions.

No randomized trial has evaluated the benefit of hospitalization


CLASS I RECOMMENDATION

1. Patients with TIA should preferably undergo neuroimaging evaluation within 24 hours of symptom onset. MRI, including DWI, is the preferred brain diagnostic imaging modality. If MRI is not available, head CT should be performed (Class I, Level B).

2. Noninvasive imaging of the cervicocephalic vessels should be performed routinely as part of the evaluation of patients with suspected TIAs (Class I, Level A )


CLASS I RECOMMENDATION

3. Noninvasive testing of the intracranial vasculature reliably excludes the presence of intracranial stenosis (Class I, Level A) and is reasonable to obtain when knowledge of intracranial steno-occlusive disease will alter management. Reliable diagnosis of the presence and degree of intracranial stenosis requires the performance of catheter angiography to confirm abnormalities detected with noninvasive testing.

4. Patients with suspected TIA should be evaluated as soon as possible after an event (Class I, Level B).


CLASS II RECOMMENDATION

1. Initial assessment of the extracranial vasculature may involve any of the following: carotid ultrasound/TCD, MRA or CTA, depending on local availability and expertise, and characteristics of the patient (Class IIa, Level B).

2. If only noninvasive testing is performed prior to endarterectomy, it is reasonable to pursue two concordant noninvasive findings; otherwise catheter angiography should be considered (Class IIa, Level B).



3. The role of plaque characteristics and detection of microembolic signals is not yet defined (Class IIb, Level B).

4. Electrocardiography should occur as soon as possible after TIA (Class I, Level B). Prolonged cardiac monitoring (inpatient telemetry or Holter monitor) is useful in patients with an unclear etiology after initial brain imaging and electrocardiography (Class IIa, Level B).



5. Echocardiography (at least TTE) is reasonable in the evaluation of patients with suspected TIAs, especially when the patient has no cause is identified by other elements of the work-up (Class IIa, Level of Evidence B). TEE is useful in identifying patent foramen ovale, aortic arch atherosclerosis, and valvular disease and is reasonable when identification of these conditions will alter management (Class IIa, Level of Evidence B).

6. Routine blood tests (complete blood count, chemistry panel, prothrombin time and partial thromboplastin time, and fasting lipid panel) are reasonable in the evaluation of patients with suspected TIAs (Class IIa, Level of Evidence B).


It is reasonable to hospitalize patients with TIA if they present within 72 hours of the event and any of the following criteria are present:

ABCD2 score of ≥3, (Class IIa, Level C).

ABCD2 score of 0-2 and uncertainty that diagnostic work-up can be completed in 2 days as an outpatient (Class IIa, Level C).

ABCD2 score of 0-2 and there is other evidence that indicates patient’s event was caused by focal ischemia (Class IIa, Level C).



Transient Ischaemic Attack (TIA)

Cranial CT

Carotid Doppler Ultrasound

Normal 30-70% stenosis +/- “non-surgical” plaque

EndarterectomyAngioplasty ± stent

Look for other sources of emboli-Echocardiogram-Holter monitor

MRA

Tests congruent

Medical Treatment

> 70% stenosis on appropriate side

MRA or CTA

Tests incongruent

Further non-invasive imaging

(do alternate test)MRA, CTA or DSA

< 70% stenosis> 70% stenosis

Tests congruent


ประวัติต่อ..

หลังกลับจากโรงพยาบาลผู้ป่วยมีอาการแขนขาด้านขวาอ่อนแรง จึงไปโรงพยาบาลอีกแห่ง 1800 น.วันเดียวกัน

ความดันเลือด 150/77 มม.ปรอท อัตราชีพจร 57 ครั้งต่อนาท ีอัตราการหายใจ 20 ครั้งต่อนาท ีอุณหภูมิกาย 37 องศาเซลเซียส ตรวจพบแขนขาด้านขวาอ่อนแรง

ให้การวินิจฉัยว่า หลอดเลือดสมองอุดตันเฉียบพลัน ได้ส่งตรวจคอมพิวเตอร์สมอง เมื่อวันที ่6 กุมภาพันธ์ พบว่ามีเนื้อสมองด้านซ้ายขาดเลือด จึงรับรักษาในโรงพยาบาล


ท่านจะให้การรักษาอย่างไร

Medical Treatment :

- Antithrombotic :Antiplatelet vs. Anticoagulant

- Statin ?

- Antihypertensive drug : who,what,where,when, how

- Life style modification

Intervention : angioplasty

Surgery : carotid endarterectomy


ANTIPLATELET AGENT RECOMMENDATION

Noncardioembolic ischemic stroke or TIA

Aspirin 50-325 mg/d monotherapy or aspirin 25 mg and ER dipyridamole 200mg twice daily after TIA for prevention future stroke.(Revised)

Clopidogrel 75 mg monotherapy for secondary prevention or aspirin 25 mg and ER dipyridamole 200mg twice daily.

ASA and clopidogrel 75 mg might be considered for initiation within 24 hours of TIA and continuation for 90 days (Class IIb, level B)(New recommendation)


INTERVENTION FOR LARGE-ARTERY ATHEROSCLEROSIS

1. TIA within past 6 mo. and ipsilateral severe (70-99%) carotid stenosis. CEA (perioperative morbidity and mortality risk <6%)(Class I,levelA)

2.Ipsilateral moderate (50-69%) carotid stenosis. CEA depend on age and comorbidities.( perioperative morbidity and mortality risk <6%)(Class I,level B)

3.Stenosis < 50%, CEA and CAS not recommended(Class III, level A)


4.Revascularization in TIA is reasonable to perform within 2 weeks (Class IIa,level B)

5.CAS is alternative to CEA for symptomatic patients at average to low risk of complication when ICA lumen reduced >70%(noninvasive imaging) or > 50%(catheter-based image)with rate of perriprocedural stroke or death <6%(Class IIa. level B)



6.CEA is considered in older patients may improved outcome, younger patients CAS is equal to CEA (risk for periprocedural complication and long-term for ipsilateral stroke)(New)(Class IIa,level B)

7.Symptomatic severe stenosis (>70%)whom increase risk for surgery, radiation-induced stenosis or restenosis after CEA, CAS (Revised)(Class IIa,level B) CEA or CAS should be performed (risk for periprocedural complication and long-term for ipsilateral stroke(Revised)(ClassI,level B)



8. Routine, long-term FU imaging of extracarotid with carotid duplex ultrasonography is not recommended. (New)(Class III, level B)

9. Recent (6mo.)TIA or ischemic stroke ipsilateral to stenosis or occlusion of middle cerebral or carotid artery,EC/IC by pass is not recommended (Class III,level A)



10.Recurrent or progressive ischemic symptoms ipsilateral to stenosis or occlusion of distal (surgical inaccessible) carotid artery,or occlusion of midcervical carotid artery after institutional of optimal medical therapy, EC/IC is considered(New)(Class IIb,level C)

11. Optimal medical therapy, antiplatelet, statin and risk factors modification is recommended for carotid artery stenosis and TIA or stroke (Class I,level A)



EXTRACRANIAL VERTEBROBASILAR DISEASE RECOMMENDATIONS

1. Preventive therapy with antithrombotic therapy, lipid lowering, BP control, lifestyle optimization in symptomatic extracranial vertebral artery stenosis (Class I,level C)

2. Endovascular stenting with extracranial vertebral stenosis have symptom despite optimal medical treatment (Class IIb,level C)

3. Open surgical procedures, including vertebral endarterec -tomy and vertebral artery transposition in symptomatic despite optimal medical treatment (Class IIb, level C)


INTRACRANIAL ATHEROSCLEROSIS

1. WASID study 569 stroke or TIA 50-99% intracranial stenosis of MCA, intracranial ICA, intracranial VA or basilar artery compared ASA 1300mg/d to warfarin (INR 2-3)

2.Antiplatelet Therapy Trials

3.Intracranial


COMPARISON OF WARFARIN AND ASPIRIN FOR SYMPTOMATIC

INTRACRANIAL ARTERIAL STENOSIS

Marc I. Chimowitz, M.B., Ch.B., Michael J. Lynn, M.S., Harriet Howlett-Smith, R.N., Barney J. Stern, M.D., Vicki S. Hertzberg, Ph.D., Michael R. Frankel, M.D., Steven R. Levine, M.D., Seemant Chaturvedi, M.D., Scott E. Kasner, M.D., Curtis G. Benesch, M.D., Cathy A. Sila, M.D., Tudor G. Jovin, M.D., and Jose G. Romano, M.D., for the Warfarin–Aspirin Symptomatic Intracranial Disease Trial Investigators*

N Engl J Med 2005;352:1305-16.


MAJOR HEMORRHAGE AND DEATH IN WASID

AspirinEvents / 100

pt.yrs

WarfarinEvents/100

pt.yrs

p-value

Major Hem. 1.8 4.4 0.01

Death 2.4 5.2 0.02


PRIMARY END POINT: STROKE AND VASCULAR DEATH

Aspirin Warfarin

No.of Patients 280 289

No. of Patients with Event 62 ( 22%) 63 (22%)

1yr / 2yr rates 15 / 21 17 / 22

Log-Rank p - value 0.830.83

Hazard Ratio (95% CI) 1.04 (0.73 – 1.48)1.04 (0.73 – 1.48)


n engl j med

352;13

www.nejm.org march

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2005

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new england journal

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the stenotic intracranial artery; and a composite ofischemic stroke, death from vascular causes otherthan stroke, or nonfatal myocardial infarction. Therewere no significant differences between the twotreatment groups in the rates of any of these endpoints (Table 2). A major cardiac event (myocardialinfarction or sudden death), which was not a pre-specified secondary end point, occurred significant-ly more frequently in the warfarin group than in theaspirin group (rate, 2.9 percent in the aspirin groupvs. 7.3 percent in the warfarin group; hazard ratio,0.40; 95 percent confidence interval, 0.18 to 0.91;P=0.02).

Adverse Events

The rate of death was significantly higher amongpatients assigned to warfarin (4.3 percent in the as-pirin group vs. 9.7 percent in the warfarin group;hazard ratio, 0.46; 95 percent confidence interval,0.23 to 0.90; P=0.02) (Table 3 and Fig. 3A). Patients

* The hazard ratio in the aspirin group as compared with the warfarin group was determined with the use of a Cox proportional-hazards regres-sion model, with treatment as the only covariate. CI denotes confidence interval.

† P values are for comparison between the aspirin group and the warfarin group and were calculated by the log-rank test. ‡ Given the number of patients recruited and the outcomes observed, if warfarin is in fact superior to aspirin by the degree hypothesized,

the probability that the study, if completed, would have resulted in a statistically significant difference in favor of warfarin

18

was 0.23.

Table 2. Primary and Secondary End Points.

Event Aspirin (N=280) Warfarin (N=289)Hazard Ratio

(95% CI)* P Value†

Patients with an Event

Probability at 1 Yr

Probability at 2 Yr

Patients with an Event

Probability at 1 Yr

Probability at 2 Yr

no. (%) no. (%)

Primary end point‡

Ischemic stroke, brain hemor-rhage, or death from vascu-lar causes other than stroke

62 (22.1) 0.15 0.21 63 (21.8) 0.17 0.22 1.04 (0.73–1.48) 0.83

Secondary end points

Ischemic stroke or brainhemorrhage

58 (20.7) 0.15 0.20 51 (17.6) 0.15 0.18 1.20 (0.82–1.75) 0.34

Ischemic stroke 57 (20.4) 0.15 0.20 49 (17.0) 0.14 0.17 1.23 (0.84–1.80) 0.29

Ischemic stroke in territory ofstenotic artery

42 (15.0) 0.12 0.15 35 (12.1) 0.11 0.13 1.26 (0.81–1.97) 0.31

Disabling or fatal ischemic stroke

25 (8.9) 0.08 0.09 18 (6.2) 0.05 0.05 1.46 (0.80–2.68) 0.22

Ischemic stroke, myocardial in-farction, or death from vas-cular causes other than stroke

66 (23.6) 0.16 0.23 71 (24.6) 0.19 0.23 0.98 (0.70–1.37) 0.90

Figure 2. Cumulative Incidence of the Primary End Point after Randomization, According to Treatment Assignment.

The primary end point was ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke.

P=0.830.4

Prob

abili

ty o

f Prim

ary

End

Poin

t

0.3

0.2

0.1

0.00 1 2 3 4 5

Aspirin

Warfarin

Years after Randomization

No. at RiskAspirinWarfarin

18 16

59 66

120 130

192 202

280 289

Copyright © 2005 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org on October 27, 2005 . This article is being provided free of charge for use in Thailand.

COMPARISON OF WARFARIN AND ASPIRIN FOR SYMPTOMATIC INTRACRANIAL ARTERIAL STENOSIS

Cumulative Incidence of the Primary End Point wasIschemic stroke, brain hemorrhage, or death

from vascular causes other than stroke.

Chimowitz MI., et al. N Engl J Med 2005;352:1305-16.Friday, August 22, 2014

WASID: ISCHEMIC STROKE IN TERRITORY OF SYMPTOMATIC ARTERY

Aspirin Warfarin

# of Patients 280 289

# Patients with Event 42 (15%) 35 (12%)

1yr / 2yr rates 12 / 15 11 / 13

Log-Rank p – value 0.310.31

Hazard Ratio (95% CI) 1.26 (0.81 – 1.97)1.26 (0.81 – 1.97)


SAMMPRIS TRIAL

Stenting and Aggressive Medical Management for

Preventing Recurrent stroke in Intracranial

Stenosis

An Investigator-initiated and Designed

NIH / NINDS Funded Trial


SAMMPRIS TRIAL

TIA or stroke in 30 days related to 70-99% stenosis of major intracranial compared aggressive medical management alone to aggressive medical management with angioplasty and stenting with Wingspan stent system (Stryker Neurovascular, Fremont, CA, USA)


90% stenosis


AGGRESSIVE MEDICAL MANAGEMENT

1. ASA 325 mg/d and clopidogrel 75mg/d for 90 days.

2. SBP <140 mmHg(<130mmHg in DM)

3. LDL-C <70mg/dl

4. Lifestyle modification program


RESULT OF 30-DAY RATE

Stopped april 2011, 451 were randomized.

Rate of stroke and death was higher in stenting arm (14.7% vs. 5,8%)(P=0.002)

2.2% stroke-related deaths in stenting arm and 0.4% in medical arm


Stenting vs. Medical Management for Intr acr anial Stenosis

n engl j med 365;11 nejm.org september 15, 2011 999

span system in high-risk patients with intracra-nial stenosis, because the rate of periprocedural stroke after PTAS was higher than expected and the rate of stroke in the medical-management group was lower than estimated. The 30-day rate of stroke or death in the PTAS group (14.7%) is substantially higher than the rates previously re-ported with the use of the Wingspan stent in the phase I trial and in two registries (rates ranging from 4.4% to 9.6%).10,20,25 The higher rate in the current study does not reflect inexperience of the operators, because most of the interventionists who participated in the registries also participat-ed in this trial, and all the interventionists in this trial were credentialed to participate on the basis of evidence of their experience. In addition, the rates of periprocedural stroke did not decline over the course of the enrollment period and did not dif-fer significantly between high-enrolling sites and low-enrolling sites in this trial.

One possible explanation for the higher rate of periprocedural stroke in this trial as compared with the registries is that all the patients in this study had stenosis of 70 to 99% and recent symptoms, whereas the registries included patients with steno-sis of 50 to 99% and symptoms that had occurred more than 30 days before enrollment. Recent symptoms may be a marker for unstable plaque, which could increase the risk of distal embolism during stenting, as has been reported with extra-cranial carotid stenting.26,27 Another explanation for the higher rate of periprocedural stroke in this trial is that the rigorous protocol for evaluating events (i.e., evaluation of all potential end points by neurologists, the adjudication process, and site-monitoring visits) could have resulted in the de-tection of some milder strokes that may not have been detected in the registries. However, the per-centage of primary end-point strokes in the PTAS group that were disabling or fatal (35%; 16 of 46 patients) is higher than the percentage of primary end-point strokes that were categorized as major in the stenting group (21%) or the endarterectomy group (28%) in a recent randomized trial involv-ing patients with extracranial carotid stenosis.28

The rate of stroke in the medical-management group was much lower than expected. Patients in the WASID trial with the same entry criteria who were treated with aspirin or warfarin and standard management of risk factors had a 30-day rate of stroke or death of 10.7% and a 1-year rate of the

primary end point of 25%.10 In contrast, the cor-responding rates in the medical-management group in this trial were 5.8% and 12.2%. Although we expected the rate of stroke to be reduced with intensive management of risk factors — on the basis of post hoc analyses from the WASID trial that suggested that lowering LDL cholesterol and systolic blood pressure could reduce the risk of stroke22,29 — we were surprised at the extent and rapidity of the reduction. It is also possible that the combination of aspirin and clopidogrel played an important role in lowering the early risk of stroke. This is supported by the results of a study of transcranial Doppler ultrasonography involving patients with recently symptomatic intracranial stenosis, which showed that aspirin and clopido-grel, as compared with aspirin alone, reduced the frequency of ipsilateral distal microemboli.30 The effect of the lifestyle modification program on the outcome can be determined only at the end

Cum

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ive!

Prob

abili

ty!o

f!the

!Prim

ary

End!

Poin

t

1.00

0.80

0.90

0.70

0.60

0.40

0.30

0.10

0.50

0.20

0.000 3 6 9 12 15

Months!since!Randomization

P=0.009

No.!at!RiskMedical manage-

ment groupPTAS group

227

224

196

182

164

153

132

125

115

98

92

83

Medical-managementgroup

PTAS group0.20

0.10

0.05

0.15

0.000 3 6 9 12 15

Figure!1.!Kaplan–Meier!Curves!for!the!Cumulative!Probability!of!the!Primary!End!Point,!According!to!Treatment!Assignment.

The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. The curves were truncated at 15 months because relatively few patients have been followed beyond this time and there have only been two primary end-point events beyond 15 months, both in the group receiving percutaneous transluminal angioplasty and stenting (PTAS) (one at 26.1 months and one at 26.2 months). The maximum duration of follow-up is 28.9 months for the group receiving medical management only and 28.1 months for the PTAS group. The inset shows the same data on an enlarged segment of the y axis.

The New England Journal of Medicine Downloaded from nejm.org on August 10, 2014. For personal use only. No other uses without permission.

Copyright © 2011 Massachusetts Medical Society. All rights reserved.

Rate of primary end point in 30-day PTAS was 16% and medical-

management group was 4.3% and 1 year were 20.9% and 12.9%,P0.028


INTRACRANIAL ATHEROSCLEROSIS RECOMMENDATION

1. TIA or stroke caused by 50-99% stenosis of major intracranial artery, ASA 325 mg/d is recommended. (Class I, level B)(Revised)

2.Recent stroke or TIA (within 30 days from severe stenosis (70-99%) of major intracranial artery, add clopidogrel 75 mg/d to aspirin for 90 days.(New)(Class IIb, level B)

STROKE OR TIA CAUSED BY 50-99% STENOSIS OF MAJOR INTRACRANIAL ARTERY


3.Data are insufficient to make a recommendation regarding the usefulness of clopidogrel alone, aggrenox, or cilostazol alone (New)(Class IIb,level C)

4.Maintain SBP <140 mmHg and high intensity statin therapy are recommended (Revised)(Class I,level B)

5.Angioplasty or stenting is not recommenced (New)(Class III,level B)

6.EC/IC bypass surgery is not recommended (Class III,levelB)



7.Stenting with wingspan stent system is not recommended as initial treatment even take antithrombotic agent(New)(Class III,level B)

8.Usefulness of angioplasty alone or placement of stent other than stenting with wingspan stent system is unknown (Revised)(Class IIb,level C)



9.Recurrent TIA or Stroke after institution of ASA and clopidogrel therapy, achievement of SBP < 140 mmHg, and high-intensity statin therapy, usefulness of angioplasty alone or placement of wingspan stent system stent other than stent is unknown (New)(Class IIb,level C)

10.Active progressing symptoms after ASA and clopidogrel therapy, usefulness of angioplasty alone or placement of wingspan stent system stent other than stent is unknown (New)(Class IIb,level C)




Noncardioembolic ischemic stroke or TIA

Aspirin 50-325 mg/d monotherapy or aspirin 25 mg and ER dipyridamole 200mg twice daily after TIA for prevention future stroke.(Revised)

Clopidogrel 75 mg monotherapy for secondary prevention or aspirin 25 mg and ER dipyridamole 200mg twice daily.

ASA and clopidogrel 75 mg might be considered for initiation within 24 hours of TIA and continuation for 90 days (Class IIb, level B)(New recommendation)


ASA and clopidogrel initiated days to years after TIA and continued for 2-3 years,increases risk of hemorrhage relative to either agent alone and is not recommended for routine long-term secondary prevention after TIA (Class I,level A)

Patients who have an ischemic stroke or TIA while taking ASA, no evidence that increasing dose of ASA provides additional benefit.

Patients with history of ischemic stroke or TIA, AF and CAD, usefulness of adding antiplatelet therapy to VKA therapy is uncertain for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular event.



THANK YOU


current treatment of transient ischemic attack

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