assessment and management of tia 2013. 12. 06 andre douen md, phd, frcpc, faha director west gta...
TRANSCRIPT
![Page 1: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/1.jpg)
Assessment and management of TIA2013. 12. 06
Andre Douen MD, PhD, FRCPC, FAHADirector West GTA Regional Stroke Program,Chief, Division of Neurology,Trillium Health Partners MississaugaCMO, Innovate R&Dwww.educatehealth.ca
Disclosures: Ad Board: BI, Sanofi-Aventis, Pfizer, BMS, BayerSpeaker: BI, BMS, Pfizer
![Page 2: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/2.jpg)
Transient ischemic attack• A forthcoming stroke is often announced by a
transient ischemic attack (TIA)
• Like ischemic strokes, TIAs are caused by vessel occlusion or reduction of blood flow
• The symptoms are the same as stroke symptoms, and may include: Impaired vision, speech disruption, weakness and numbness
• TIAs are brief due to early revascularization/ reperfusion
Johnston et al. National Stroke Association. Ann Neurol 2006; 60: 301–13.
![Page 3: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/3.jpg)
The work-up and management is similar to a stroke
• Etiology not different from definite stroke
• Clinically < 24-hour duration, but....
• New MRI lesions seen in up to 80% of patients with clinical course of TIA
• Frequently followed by more severe stroke
• TIA and stroke have a similar risk for early recurrent stroke, ~ up to 14% within the first 2 weeks
• Opportunities for prevention – Rapid W/U in SPC
Johnston et al. JAMA 2000; 284: 2901–2906.Warach, Kidwell. Neurology 2004; 62: 359–360.
Mohr. Neurology 2004; 62 (8 Suppl 6): S3–S6.
![Page 4: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/4.jpg)
Case 1 Mrs W.S., LLM
• 62 y/o obese lawyer with GERD
• PMH:o Smoking 1ppd x 30 yrso No HTN, No DM, No Cholesterol at her
last visit in Jan 2010
Douen
![Page 5: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/5.jpg)
Case 1 Mrs W.S.• HPI
o Speaking with niece regarding a legal matter when..
o Slurred speech Loss of speecho Right facial droop, Right arm weak and
incoordinated
• EMS o Symptoms resolved with 15 mino Patient declines transfer to ERo Elects to wait overnight and call fam doc
in AM for a quick visit and head to office after to prepare for prosecuting a medico-legal case Douen
![Page 6: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/6.jpg)
CaseExamination in office the next day:
BP = 160/90 ; HR 90 and regular. No neurological deficits, but with right carotid bruit
Current Meds: Losec, Tylenol prn for back pain
Next steps:– DDX ? [Is this a TIA, if not what could it be ?]– If TIA, what’s her risk of recurrent stroke ? – Is there a tool that can help assess this ? – What investigations is needed now ?– What should I do...panic ? [Will I get sued if I make
the wrong decision ? ]– Should I start Meds ?– Maybe the ER might be a safe bet ?
![Page 7: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/7.jpg)
Stroke/TIA Mimics• Migraine (aura)• Vertigo • Syncope (vaso-vagal, cardiogenic, metabolic)• Seizure (simple, CPSz, grand mal with “Todd’s”)• Structural brain lesions (tumors, AVM, subdurals,
abscess)• Radiculopathies (focal numb/weak)• Neuropathies (focal (CTS, ulnar, radial) or diffuse
numb ± weak)• Dementia (confusion)• Neuroses• Stress/Anxiety• Malingering
![Page 8: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/8.jpg)
Case 1 Mrs W.S.
• Needs to get back to office ASAP• Thinks this “TIA” thing is non-sense, as she
feels she was a bit stressed over the case and that caused her symptoms
• Not keen on extensive investigations for such a minor episode
• She might comply if she can schedule these in between her practice over the next 2 months
• If it was a “TIA” (she is skeptical) then she wants to estimate her risk of recurrence
Douen
![Page 9: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/9.jpg)
1. What do you think her stroke risk might be within the next month:a) ~ 2%
b) ~ 8%
c) ~ 20%
d) She’ll almost certainly re-stroke
e) Her risk can only be measured over 3 months
![Page 10: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/10.jpg)
1. What do you think her stroke risk might be with in the next month:a) ~ 2%
b) ~ 8%
c) ~ 20%
d) She’ll almost certainly re-stroke
e) Her risk can only be measured over 3 months
![Page 11: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/11.jpg)
Stroke Recurrence
• Antecedent stroke/TIA is the most significant indicator of a possible recurrent stroke
• High incidence of early recurrent stroke following either TIA or minor stroke
• Early recognition and treatment significantly reduces the risk of stroke recurrence
Johnston et al. JAMA 2000; 284: 2901–2906.Warach, Kidwell. Neurology 2004; 62: 359–360.
Mohr. Neurology 2004; 62 (8 Suppl 6): S3–S6.
![Page 12: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/12.jpg)
Nearly 1 in 5 stroke/TIA patients is at risk of a recurrent event within 3 months
0
5
20
15
10
7-daystroke risk
30-daystroke risk
3-monthstroke risk
Str
oke
pat
ien
ts (
%)
0
5
20
15
10
7-daystroke risk
30-daystroke risk
3-monthstroke risk
TIA
pat
ien
ts (
%)
Stroke patients: risk of recurrent event TIA patients: risk of recurrent event
Coull et al. BMJ 2004; 328: 326.
11.5
15.0
18.5
8.0
11.5
17.3
![Page 13: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/13.jpg)
The ABCD2 Score
Indicator Criteria Score
A Age 1 point for age 60 /1B Blood pressure 1 point for BP >140/90 mmHg /1
C Clinical features2 points for focal weakness or1 point for speech disturbance
/2
D Duration of symptoms1 point for duration 10-59 minutes2 points for duration >60 minutes
/2
D Diabetes 1 point for presence of diabetes /1 Total Score /7
![Page 14: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/14.jpg)
The ABCD2 Score
Indicator Criteria Score
A Age 1 point for age 60 /1B Blood pressure 1 point for BP >140/90 mmHg /1
C Clinical features2 points for focal weakness or1 point for speech disturbance
/2
D Duration of symptoms1 point for duration 10-59 minutes2 points for duration >60 minutes
/2
D Diabetes 1 point for presence of diabetes /1 Total Score /7
1
1
2
1
0
5
![Page 15: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/15.jpg)
Risk Factors for Stroke Within 90 Days of a TIAThe ABCD2 Score
0
5
10
15
20
25
0 1 2 3 4 5 6 7
2 Days7 Days30 Days90 Days
StrokeRisk(%)
ABCD2 Score
LowRisk
HighRisk
IntermediateRisk
Lancet 2007;369:283-92.
![Page 16: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/16.jpg)
Risk of recurrent events during the 7 days after a TIA stratified by ABCD2 score
Chandratheva A et al. Stroke 2010;41:851-856Copyright © American Heart Association
![Page 17: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/17.jpg)
Case 1 Mrs W.S.
• After reviewing ABCD2 and showing her these charts, she is now more agreeable to comply with investigations
• She wants to know, how do stroke and TIA occur, and also what investigations she would need
• She also wants to know about how soon she can have the studies completed
• She will reluctantly cancel appointments to attend these investigations
• What can she take to prevent this from recurring?
Douen
![Page 18: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/18.jpg)
Douen
(Anticoagulation)
Antiplatelet
Pathophysiology: Multiple Mechanisms requiring urgent W/U
![Page 19: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/19.jpg)
Case
Next steps:– DDX ? [Is this a TIA, if not what could it be ?]– If TIA, what’s her risk of recurrent stroke ? – Is there a tool that can help assess this ? – What investigations are needed now ? How soon ?– What should I do...panic ? [Will I get sued if I make
the wrong decision ? ]– Should I start Meds ?– Maybe the ER might be a safe bet ?
![Page 20: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/20.jpg)
What investigations would you consider for this patient (why, when)?
ECHO (TEE,TTE) Routine labs Carotid doppler CT scan ECG, Echo (TTE/TEE) Holter Angiogram (CTA / MRA)
![Page 21: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/21.jpg)
Stroke Types and Incidence
Ischemic stroke 85-88%
Hemorrhagic stroke 12-15%Other
5%
Cryptogenic30%
Cardiogenicembolism
20%
Small vesseldisease
“lacunes” 25%
Atheroscleroticcerebrovascular
disease20%
Albers GW, et al. Chest 2004; 126 (3 Suppl): 438S–512SMcGrath et al. Stroke 2012; 43: 2048-2054.
Boehringer Ingelheim (Canada) Ltd. cannot recommend the use of products outside the Canadian approved Product Monograph.The content of this slide may contain information not reviewed by Health Canada.
![Page 22: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/22.jpg)
2. What priority would you give these investigations?
a) ECG > ECHO> Telemetry/Holter>Carotid Doppler>CT
b) CT>Telemetry/Holter>ECHO>Carotid Doppler> ECG
c) ECHO > Holter > CT>Carotid Doppler > ECG
d) CT> Carotid Doppler = ECG > Holter > ECHO
e) CT = ECG = Carotid Doppler > Holter > ECHO
![Page 23: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/23.jpg)
2. What priority would you give these investigations?
a) ECG > ECHO> Telemetry/Holter>Carotid Doppler>CT
b) CT>Telemetry/Holter>ECHO>Carotid Doppler> ECG
c) ECHO > Holter > CT>Carotid Doppler > ECG
d) CT> Carotid Doppler = ECG > Holter > ECHO
e) CT = ECG = Carotid Doppler > Holter > ECHO
![Page 24: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/24.jpg)
Cardioemboli
• AF: High incidence of paroxysmal AF in acute stroke 13.5% detection of new onset AF using a
combination of serial ECG daily x 3 days plus Holter Overall ~20 % of acute stroke patient with AF.
(Douen et al, Stroke 2008)
• Up to 3 million people worldwide suffer strokes related to AF each year1-3
1. Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf
2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 2. 1991:22(8);983-8
3. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996;27:1760-4
![Page 25: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/25.jpg)
EMBRACE
Prolonged Ambulatory Cardiac Monitoring Improves the Detection and Treatment of Atrial Fibrillation in Patients with Cryptogenic Stroke: Primary Results from the EMBRACE Multicenter Randomized Trial Gladstone DJ, International Stroke Conference, Honolulu, 2013
n=572 (age 73±9yrs;); recent ischemic cryptogenic stroke/TIA, no known AF; 16 stroke centers
Randomized to wear either an event-triggered cardiac monitor up to 30 days or a repeat 24 h Holter
New AF detected among 16% of 30-day monitoring group, vs. 3% in the Holter group (p<0.001)
Presented by: Gladstone DJ, International Stroke Conference, Honolulu, HI
30-day Holter0%
2%
4%
6%
8%
10%
12%
14%
16%
18%16%
3%
New AF
P<0.001
![Page 26: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/26.jpg)
Case
Next steps:– DDX ? [Is this a TIA, if not what could it be ?]– If TIA, what’s her risk of recurrent stroke ? – Is there a tool that can help assess this ? – What investigations are needed now ? How soon ?– What should I do...panic ? [Will I get sued if I make
the wrong decision ? ]– Should I start Meds ?– Maybe the ER might be a safe bet ?
![Page 27: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/27.jpg)
3. Which of the following statements about the management of patients with TIA or minor stroke are correct:a. If possible work-up should be completed within 2-3
days
b. Early treatment and intervention could reduce stroke recurrence by 80%
c. Early management through a stroke clinic is likely superior to routine out patient management.
d. For those with ipsilateral severe stenosis revascularization is recommended within 2 weeks
e. All of the above
![Page 28: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/28.jpg)
3. Which of the following statements about the management of patients with TIA or minor stroke are correct:a. If possible work-up should be completed within 2-3
days
b. Early treatment and intervention could reduce stroke recurrence by 80%
c. Early management through a stroke clinic is likely superior to routine out patient management.
d. For those with ipsilateral severe stenosis revascularization is recommended within 2 weeks
e. All of the above
![Page 29: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/29.jpg)
EXPRESSUrgent treatment of TIA and minor stroke
Outcome Phase 1 Phase 2
Time to clinic visit - 3 days ( 2 -5) 1 day (0-3)
Time to prescription- *20 days (8 -53) 1 day (0-3)
90 day risk of stroke- ~10.3% 2.1%**
*No prescriptions given. Patients advised to see family MD
** 80% reduction in risk of recurrent stroke
![Page 30: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/30.jpg)
Timeliness of Care In Patients with TIA The OXVASC Study
Neurology 2005;65:371-5.
Neurology 2005;65:371-5.c
![Page 31: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/31.jpg)
The Consequences of Delaying Access to CareThe OXVASC Study
Neurology 2005;65:371-5.
Stroke Patients
Neurology 2005;65:371-5.c
![Page 32: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/32.jpg)
30.2
14.817.6
3.3
11.4
4
8.9
-2.9
-10
0
10
20
30
40 70-99% Stenosis
50-69% Stenosis
0-2 4-122-4 >12
Time From Event to Randomization (weeks)
5 Year ARRIn Stroke
(%)
Timing of Surgical InterventionThe NASCET and ECST Studies
Lancet 2004;363:915-24.
![Page 33: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/33.jpg)
CaseNext steps :
– DDX ? [Is this a TIA, if not what could it be ?]
– If TIA, what’s her risk of recurrent stroke ?
– Is there a tool that can help assess this ?
– What investigations are needed now ? How soon ?
– What should I do...panic ? [Will I get sued if I make the wrong decision ? ]
– Should I start Meds ?
– Maybe the ER might be a safe bet ?
![Page 34: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/34.jpg)
Stroke / TIA
Medical
Risk factor management
Interventional
Revascularization
CEA vs Stent
Antiplatelet Anticoagulant
Antithrombotic
![Page 35: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/35.jpg)
4. Following and ischemic stroke it is best to wait 3 - 4 days before initiating antiplatelet therapy because of increased risk of bleeding.a. True
b. False
![Page 36: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/36.jpg)
4. Following and ischemic stroke it is best to wait 3 - 4 days before initiating antiplatelet therapy because of increased risk of bleeding.a. True
b. False
![Page 37: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/37.jpg)
5. In an ASA naive patient which of the following Antitrhombotic agents is recommended for secondary prevention of Non-Cardioembolic stroke
a. ASA
b. ASA/ER Dipyridamole
c. Clopidogrel
d. Clopidogrel + ASA
e. Warfarin
f. Either b) or c)
g. Any of a) , b) or c)
![Page 38: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/38.jpg)
5. In an ASA naive patient which of the following Antitrhombotic agents is recommended for secondary prevention of Non-Cardioembolic stroke
a. ASA
b. ASA/ER Dipyridamole
c. Clopidogrel
d. Clopidogrel + ASA
e. Warfarin
f. Either b) or c)
g. Any of a) , b) or c)
![Page 39: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/39.jpg)
Prevention of Vascular Events in Stroke/TIA Patients with ASA Following First Stroke
ASA vs. Placebo: Efficacy by Dose*
ASA Dose Relative Risk of Vascular Events**
1,000 – 1,300 mg/d
300 mg/d
50 – 75 mg/d
Overall
0.8†
ASA better Placebo better
* A meta-analysis of 10 controlled trials comparing acetylsalicylic acid (ASA) with placebo. ** Vascular events comprise stroke, MI, or vascular death.† Signifies a 20% relative risk reduction
Adapted from Albers GW et al. Neurology. 1999; 53(suppl 4): S25-S38.
![Page 40: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/40.jpg)
![Page 41: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/41.jpg)
6. For patients already on ASA which of the following Antitrhombotic agents is recommended for secondary prevention of Non-Cardioembolic stroke
a. ASA
b. ASA/ER Dipyridamole
c. Clopidogrel
d. Clopidogrel + ASA
e. Warfarin
f. Either b) or c)
g. Any of a) , b) or c)
![Page 42: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/42.jpg)
6. For patients already on ASA which of the following Antitrhombotic agents is recommended for secondary prevention of Non-Cardioembolic stroke
a. ASA
b. ASA/ER Dipyridamole
c. Clopidogrel
d. Clopidogrel + ASA
e. Warfarin
f. Either b) or c)
g. Any of a) , b) or c)
![Page 43: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/43.jpg)
Clopidogrel + Placebo (n=3,781)
Nu
mb
er (
n/%
) w
ith
eve
nt
MATCH: Bleeding Complications Increased Significantly
Life-threateningbleeding
0
20
40
60
80
100
Majorbleeding
Minorbleeding
Clopidogrel + ASA (n=3,759)
96 (3%)
49 (1%)
73 (2%)
22 (1%)
120 (3%)
39 (1%)
120
Diener et al. Lancet 2004; 364: 331–337.
p<0·0001
p<0·0001
p<0·0001
![Page 44: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/44.jpg)
0.0
0.01
0.02
0.03
0.04
0.0 0.5 1.0 1.5
OAC
Clopidogrel+ASA
Major BleedingC
um
ula
tive
Ha
zard
Rat
es
Years
# at RiskC+A 3335 3172 2403 914OAC 3371 3212 2423 901
2.4 %/year
2.2 %/year
RR = 1.06
P = 0.67
![Page 45: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/45.jpg)
7. For patients already on Clopidogrel which of the following Antithrombotic agents is recommended for secondary prevention of Non-Cardioembolic stroke
a. ASA/ER Dipyridamole
b. Clopidogrel
c. Clopidogrel + ASA
d. Warfarin
e. Either a) or b)
![Page 46: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/46.jpg)
7. For patients already on Clopidogrel which of the following Antithrombotic agents is recommended for secondary prevention of Non-Cardioembolic stroke
a. ASA/ER Dipyridamole
b. Clopidogrel
c. Clopidogrel + ASA
d. Warfarin
e. Either a) or b)
![Page 47: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/47.jpg)
Case
CT brain: Nil acute
ECG: AF with HR of 95
Is a Doppler still required ??
Meds: …. ???
What is incidence of AF in acute stroke ??
![Page 48: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/48.jpg)
Case
CT brain: Nil acute
ECG: AF with HR of 95
Is a Doppler still required ?? YES
Meds: …. ???
What is incidence of AF in acute stroke ??
![Page 49: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/49.jpg)
Stroke / TIA
Medical
Risk factor management
Interventional
Revascularization
CEA vs Stent
Antiplatelet Anticoagulant
Antithrombotic
![Page 50: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/50.jpg)
Cardioemboli
• AF: o High incidence of paroxysmal AF in acute strokeo 13.5% detection of new onset AF using a
combination of serial ECG daily x 3 days plus Holtero Overall ~20 % of acute stroke patient with AF
(Douen et al, Stroke 2008)
• Up to 3 million people worldwide suffer strokes related to AF each year1-3
1. Atlas of Heart Disease and Stroke, World Health Organization, September 2004. Viewed at http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf
2. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 2. 1991:22(8);983-8
3. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation: the Framingham study. Stroke 1996;27:1760-4
![Page 51: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/51.jpg)
EMBRACE
Prolonged Ambulatory Cardiac Monitoring Improves the Detection and Treatment of Atrial Fibrillation in Patients with Cryptogenic Stroke: Primary Results from the EMBRACE Multicenter Randomized Trial Gladstone DJ, International Stroke Conference, Honolulu, 2013
n=572 (age 73±9yrs;); recent ischemic cryptogenic stroke/TIA, no known AF; 16 stroke centers
Randomized to wear either an event-triggered cardiac monitor up to 30 days or a repeat 24 h Holter
New AF detected among 16% of 30-day monitoring group, vs. 3% in the Holter group (p<0.001)
Presented by: Gladstone DJ, International Stroke Conference, Honolulu, HI
30-day Holter0%
2%
4%
6%
8%
10%
12%
14%
16%
18%16%
3%
New AF
P<0.001
![Page 52: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/52.jpg)
AF increases the risk of stroke
• AF is associated with a pro-thrombotic stateo ~5- 17 fold increase in stroke risk
• Risk of stroke is the same in patients with chronic of PAF2,3
• There is a high 30-day mortality (~25%) following cardioembolic stroke4
• AF-related stroke has a 1-year mortality of ~50%5
1. Wolf PA, et al. Stroke 1991;22:983-988; 2. Rosamond W et al. Circulation. 2008;117:e25–146; 3.Hart RG, et al. J Am Coll Cardiol 2000;35:183-187; 4. Lin H-J, et al. Stroke 1996; 27:1760-1764; 5. Marini C, et al. Stroke 2005;36:1115-1119.
![Page 53: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/53.jpg)
Stroke Severity in Patients with AF
Gladstone DJ et al. Stroke. 2009; 40:235-240
Effect of first ischemic stroke in patients with AF (n=597)%
of
pati
ents
Disabling(discharge mRS ≥ 2)
Fatal
60%
40%
0%
50%
30%
20%
10%
59.7%
20%
mRS=modified Rankin ScaleAF=atrial fibrillation
![Page 54: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/54.jpg)
Ischemic Stroke Associated With AF is Typically More Severe Than Stroke due to Other Etiologies
% b
edri
dden p
ati
ents
on a
dm
issi
on (
mR
s* =
5)
(P < 0.0005)
40
30
20
10
0
50
41.2%
23.7%
With AF Without AF
Dulli DA, et al. Neuroepidemiology. 2003;22:118-123.
Odds ratio for bedridden state following stroke due to AF was 2.23 (95% CI, 1.87-2.59; P < 0.0005)
*mRS=modified Rankin ScaleAF=atrial fibrillation
![Page 55: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/55.jpg)
Increased mortality after ischemic stroke in patients with AF persists for up to 8 years
•Population-based study of 3530 patients with ischaemic stroke•Marini C et al. Stroke 2005;36:1115–9
Patients with AF (n=869)
Patients without AF (n=2661)
Years after stroke
An
nu
al m
ort
alit
y ra
te (
%)
0
10
20
30
40
50
60 Mortality
1 2 3 4 5 6 7 8
![Page 56: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/56.jpg)
AF associated with increased risk of recurrent stroke
Marini C et al. Stroke 2005;36:1115–9
Patients with AF
Patients without AF
Recurrent stroke after ischemic stroke
Months after first stroke
Cu
mu
lati
ve p
rob
abili
ty
of
recu
rren
ce (
%)
10
12
8
6
4
2
00 2 4 6 8 10
P=0.0398
![Page 57: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/57.jpg)
Missed Opportunities for Stroke Prevention in AF:Registry of the Canadian Stroke Network 2003-2007
Gladstone Stroke 2009;40:235
No antithrombotics Dual antiplatelets Single antiplatelet Warfarin: therapeutic Warfarin: sub-therapeutic
Preadmission medications in patients with known AF admitted with acute
ischemic stroke (high-risk cohort, n=597)
Preadmission medications in patients with known AF and a previous ischemic
stroke/TIA admitted with acute ischemic stroke
(very high-risk cohort, n=323)
Need for greater efforts to prescribe and monitor appropriate antithrombotic therapy to prevent stroke in patients with AF
![Page 58: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/58.jpg)
9. The patients who benefit the most from warfarin therapy are those with AF in the age group 65-75 and with no other medical issues. OAC (e.g. warfarin) is not beneficial for the elderly
True
False
![Page 59: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/59.jpg)
9. The patients who benefit the most from warfarin therapy are those with AF in the age group 65-75 and with no other medical issues. OAC (e.g. warfarin) is not beneficial for the elderly
True
False
![Page 60: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/60.jpg)
AF prevalence increases with age
1. Go AS, et al. JAMA 2001;285:2370-2375.Age
AF
pre
va
len
ce
(%)
General population
>60 years >80 years
9
8
7
6
5
4
3
2
1
0
![Page 61: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/61.jpg)
10. Patients with AF who has spontaneous intracranial hemorrhage while using OAC should never be placed back on OAC
True
False
![Page 62: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/62.jpg)
10. Patients with AF who have spontaneous intracranial hemorrhage while using OAC should never be placed back on OAC True False
Cause of bleed needs to be assessed: Elevated INR Concomitant use of antiplatelet agent Overdose of NOAC CrCl Drug abuse H/o trauma/fall HGB, plts etc Risk benefit ratio
![Page 63: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/63.jpg)
CHADS 2
CHADS2 Score* Stroke rate
0 1.9 (1.2 -3.0)
1 2.8 (2.0-3.8)
2 4.0 (3.1-5.1)
3 5.9 (4.6-7.3)
4 8.5 (6.3 -11.1)
5 12.5 (8.2-17.5)
6 18.2 (10.5-17.4)
*Score 0: Patients can be administered aspirin*Score 1: Patients can be on aspirin and anticoagulant therapy*Score ≥2: Patients should be on anticoagulant therapy
• 1 point for Congestive Heart Failure
• 1 point for Hypertension
• 1 point for Age ≥ 75 years• 1 point for Diabetes Mellitus • 2 points for Prior Stroke or
TIA
![Page 64: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/64.jpg)
CHA2DS2-VASc Score
• 1 point for Congestive Heart Failure/LV Dysfunction
• 1 point for Hypertension
• 2 points for Age ≥ 75 years
• 1 point for Diabetes Mellitus
• 2 points for Prior Stroke or TIA1 or TE2
• 1 point for Vascular Disease3
• 1 point for Age 65-74 years
• 1 point for Sex category (female gender)
CHA2DS2-VASc Score*
One year event rate (95% CI) of hospital admission and death due to thromboembolism† per 100 person
year
0 0.78 (0.78 – 1.04)
1 2.01 (1.70 – 2.36)
2 3.71 (3.36 – 4.09)
3 5.92 (5.53 – 6.34)
4 9.27 (8.71 – 9.86)
5 15.26 (14.35 – 16.24)
6 19.74 (18.21 – 21.41)
7 21.5 (18.75 – 24.64)
8 22.38 (16.29 – 30.76)
9 23.64 (10.62 – 52.61)
*Score 0: Patients can be administered aspirin*Score 1: Patients can be administered aspirin or anticoagulant therapy*Score ≥2: Patients should be administered anticoagulant therapy†Includes peripheral artery embolism, ischemic stroke, and pulmonary embolism
1TIA = Transient ischemic attack; 2TE = Thromboembolism3Prior myocardial infarction, peripheral artery disease, aortic plaque1. Lip GY et al. Chest 2010;137:263-272
2. Olesen JB, et al. BMJ 2011;342:d1243. Task Force or the Management of Atrial Fibrillation of the ESC.
Eur Heart J 2010;31:236902429
CHA2DS2-Vasc score Mrs W.S. = 4 (hypertension, age 65-74 yr, female)
![Page 65: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/65.jpg)
CCS 2012 Update to AF Guidelines
CHADS2 = 0
*Aspirin is a reasonable alternative in some as indicated by risk/benefit
CHADS2 = 1 CHADS2 ≥ 2
No anti-thrombotic
Assess Thromboembolic Risk (CHADS2)
No additional
risk factors for stroke
Increasing stroke risk
ASA OAC* OAC* OAC*
Either female sex or vascular
disease
Age ≥ 65 yrs or combination
of female sex and vascular
disease
*OAC = Oral anticoagulant ASA = Aspirin
Consider stroke risk vs. bleeding risk
Only when the stroke risk is low and bleeding risk is high does the risk/benefit ratio favor no antithrombotic therapy
1. Skanes AC, et al. Can J Cardiol 2012;28:125-136.
![Page 66: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/66.jpg)
Case - Paul
Mrs W.S. Risk: 62-year-old - < 75 : 0HTN : 1No h/o CHF : 0No DM : 0TIA symptoms : 2
CHADS Risk = 3
CHADS-VASC Risk = 4 (HTN, F, Stroke symptoms)
![Page 67: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/67.jpg)
11. For patient with cardioembolic (AF) stroke/TIA which of the following Antitrhombotic Agents is recommended for secondary prevention
a. Warfarin
b. Dabigatran (Pradax)
c. Rivaroxaban (Xaralto)
d. Apixaban (Eliquis)
e. Clopidogrel + ASA
f. ASA/ER Dipyridamole
![Page 68: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/68.jpg)
11. For patient with cardioembolic (AF) stroke/TIA which of the following Antitrhombotic Agents is recommended for secondary prevention
a. Warfarin
b. Dabigatran (Pradax)
c. Rivaroxaban (Xarelto)
d. Apixaban (Eliquis)
e. Clopidogrel + ASA
f. ASA/ER Dipyridamole
![Page 69: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/69.jpg)
1. Haas S. J Thromb Thrombolysis. 2008;25:52-60.2. Adapted from Ezekowitz MD et al. Mayo Clin Proc. 2004;79:904-913.
Narrow efficacy window + multiple interactions
Challenges of Oral Anticoagulation Therapy (OAC)
hard to use/take1=
ISCHEMIC STROKE INTRACRANIAL BLEED
Od
ds
Rat
io
05.0 6.0 8.0
INR
1.0 2.0 3.0 4.0 7.0
5.0
15.0
10.0
1.0
20.0
![Page 70: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/70.jpg)
INR control: clinical trials v. clinical practice
INR* control in clinical trial versus clinical practice (TTR**)
1. Kalra L, et al. BMJ 2000;320:1236-1239 * Pooled data: up to 83% to 71% in individualized trials; 2. Matchar DB, et al. Am J Med 2002; 113:42-51.
** TTR = Time in Therapeutic Range (INR2.0-3.0)
66%
44%
9%
18%
38%
25%
<2.0 2.0 – 3.0 >3.0 INR
% o
f e
ligib
le p
ati
en
ts
rec
eiv
ing
wa
rfa
rin
Clinical trial1
Clinical practice2
*INR = International normalized ratio
![Page 71: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/71.jpg)
12. Despite the challenges of using warfarin, the lack of antidote for the NOAC makes them less valuable than warfarin in cardioembolic prophylaxis in acute stroke
True
False
![Page 72: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/72.jpg)
12. Despite the challenges of using warfarin, the lack of antidote for the NOAC makes them less valuable than warfarin in cardioembolic prophylaxis in acute stroke
True
False
![Page 73: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/73.jpg)
New OAC• Dabigatran Etexilate (Direct thrombin inhibitor)
in Atrial Fibrillation (RE-LY)
• Rivaroxaban (Factor Xa inhibitor)in Atrial Fibrillation (ROCKET-AF)
• Apixaban (Factor Xa inhibitor)in Atrial Fibrillation (AVERROES; ARISTOTLE)
• Dabigatran Etexilate (Direct thrombin inhibitor) in Atrial Fibrillation (RE-LY)
• Rivaroxaban (Factor Xa inhibitor)in Atrial Fibrillation (ROCKET-AF)
• Apixaban (Factor Xa inhibitor)in Atrial Fibrillation (AVERROES; ARISTOTLE)
Pros: No MonitoringRapid onset of actionSimilar or better bleeding profile to warfarin
Con: No antidote, no clear way of measuring effect
![Page 74: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/74.jpg)
Prevention of Stroke
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
0.50 0.75 1.00 1.25 1.50
Dabigatran 110 mg BID
Dabigatran 150 mg BID
HR (95% CI)Warfarin betterComparator better
Rivaroxaban 20 mg QD
Apixaban 5 mg BID
Stroke or Systemic Embolism
Ischemic StrokeDabigatran 110 mg BID
Dabigatran 150 mg BID
Rivaroxaban 20 mg QD
Apixaban 5 mg BID
Superiorityp-value
0.29<0.001 0.12 0.01
0.350.03 0.59
0.42
0.90
0.65
1.11
0.76
0.88
0.79
0.94
0.92
Cross-trial comparisons must be interpreted with caution due to differing methodologies and patient populations.
![Page 75: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/75.jpg)
Reducing the Bleeding Risk
HR (95% CI)Warfarin betterComparator better
0.50 0.75 1.00 1.250.25
Dabigatran 110 mg BID
Dabigatran 150 mg BID
Rivaroxaban 20 mg QD
Apixaban 5 mg BID
Intracranial Hemorrhage
ISTH Major BleedingDabigatran 110 mg BID
Dabigatran 150 mg BID
Rivaroxaban 20 mg QD
Apixaban 5 mg BID
Superiorityp-value
<0.001
<0.001
0.02 <0.001
0.0030.31 0.58
<0.001
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
0.80
0.93
0.30
0.41
0.67
0.42
1.04
0.69
Cross-trial comparisons must be interpreted with caution due to differing methodologies and patient populations.
![Page 76: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/76.jpg)
AF Trials: Elements of Primary Endpoint:*Annual Event Rates
0.92
1.210.97 1.05
1.401.52
0.10
0.38
0.240.47
0.260.44
0.15
0.10
0.09
0.100.04
0.19
0
0.5
1
1.5
2
2.5
3Systemic EmbolismHemorrhagic StrokeIschemic/Unspecified Stroke
Dabi 150 mg Warfarin Apixaban Warfarin Rivaroxaban Warfarin
RELY ARISTOTLE ROCKET AF
%/y
ear
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
In recent trials, the majority of AF strokes were ischemic
Cross-trial comparisons must be interpreted with caution due to differing methodologies and patient populations.
†
*Patients experiencing multiple endpoints are included in multiple categories.†Systemic embolism result reported for RELY refers to pulmonary embolism.
![Page 77: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/77.jpg)
CCS 2012 Update to AF Guidelines
When oral anticoagulant therapy is indicated, most patients should receive dabigatran, rivaroxaban, or apixaban, in
preference to warfarin
• Dabigatran and apixaban have greater efficacy and rivaroxaban has similar efficacy for stroke prevention
• Dabigatran and rivaroxaban have no more major bleeding and apixaban has less
• All three new oral anticoagulants have less intracranial hemorrhage and are much simpler to use
1. Skanes AC, et al. Can J Cardiol 2012;28:125-136.
![Page 78: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/78.jpg)
Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage
Despite Anticoagulant Reversal
Dowlatshahi D, et al. Stroke 2012. DOI: 10.1161/STROKEAHA.112.652065
![Page 79: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/79.jpg)
Hematoma Growth
Significant hematoma growth despite INR correction with PCC.
This patient was treated with 1000 U of PCC and 10 mg vitamin K 98 minutes after baseline CT scan.
Repeat INR was 1.3, 42 minutes after PCC treatment and 1.2 the next day.
INR = international normalized ratio;
PCC = prothrombin complex concentrate
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
![Page 80: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/80.jpg)
Poor Outcomes
Intracranial hemorrhage type Number In-hospital mortality*
Discharge mRS(Median IQR)†
Intraparenchymal 71 30 (42.3%) 5 (3)‡
Subdural 61 21 (34.4%) 3 (4)§
Epidural 1 0 3
Subarachnoid 8 1 (12.5%) 3 (3)
ICH = intracranial hemorrhage; mRS = modified Rankin Scale; IQR = interquartile range
*P = 0.3; †P=0.012; ‡mRS missing in 9; §mRS missing in 2
Outcome by anticoagulant-associated ICH
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
![Page 81: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/81.jpg)
30 Day Mortality Associated with Intracranial vs Extracranial Bleeds
• Data from The AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study- a cohort of 13,559 adults with diagnosed nonvalvular atrial fibrillation who received care within Kaiser Permanente of Northern California, a large integrated
• health care delivery system. Risk of death 30 days after hospitalization for warfarin-associated intracranial hemorrhage versus major extracranial hemorrhage; 95% confidence intervals (CIs) (vertical bars). P value refers to the chi-square comparison of mortality rate of intracranial versus extracranial hemorrhage.
Fang et al, The American Journal of Medicine (2007) 120, 700-705
Intracranial Extracranial0
20
40
60
80
100
48.6
5.1
IntracranialExtracranial
Mo
rta
lity
at 3
0 d
ays
(%
)
P<0.001
![Page 82: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/82.jpg)
• Prothrombin complex concentrates (PCC) therapy rapidly corrected INR in the majority of patients with anticoagulant-associated ICH, yet mortality and morbidity rates remained high
• Outcomes after anticoagulant-associated ICH can be devastating even with a reversal strategy
Conclusion
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
![Page 83: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/83.jpg)
12. Despite the challenges of using warfarin, the lack of antidote for the NOAC makes them less valuable than warfarin in cardioembolic prophylaxis in acute stroke
True
False
![Page 84: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/84.jpg)
Stroke / TIA
Medical
Risk factor management
Interventional
Revascularization
CEA vs Stent
Antiplatelet Anticoagulant
Antithrombotic
![Page 85: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/85.jpg)
ASA naive patients vs those previously on ASA
a. ASA
b. ASA/ER Dipyridamole
c. Clopidogrel
________________________
d. Warfarin
e. Clopidogrel + ASA
Antiplatelet choices – Summary Non-cardioembolic stroke
![Page 86: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/86.jpg)
Stroke / TIA
Medical
Risk factor management
Interventional
Revascularization
CEA vs Stent
Antiplatelet Anticoagulant
Antithrombotic
![Page 87: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/87.jpg)
For patient with cardioembolic (AF) stroke/TIA
a. Warfarinb. Dabigatran (Pradax)c. Rivaroxaban (Xarelto)d. Apixaban (Eliquis)_______________________e. Clopidogrel + ASAf. ASA
![Page 88: Assessment and management of TIA 2013. 12. 06 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology,](https://reader035.vdocuments.net/reader035/viewer/2022081603/56649cef5503460f949bcfa8/html5/thumbnails/88.jpg)