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Andre Douen MD , PhD, FRCPC, FAHA Director West GTA Regional Stroke Program,

The Big Deal About Mini-Strokes: Treating TIA. 2012. 12. 07. Andre Douen MD , PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology, Trillium Health Centre, Mississauga. Disclosures: Ad Board: BI, Sanofi -Aventis, BMS, Bayer Speaker: BI, BMS.

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Andre Douen MD , PhD, FRCPC, FAHA Director West GTA Regional Stroke Program,

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  1. The Big Deal About Mini-Strokes: Treating TIA 2012. 12. 07 Andre Douen MD, PhD, FRCPC, FAHA Director West GTA Regional Stroke Program, Chief, Division of Neurology, Trillium Health Centre, Mississauga Disclosures: Ad Board: BI, Sanofi-Aventis, BMS, Bayer Speaker: BI, BMS

  2. So…what is the big deal ? OrShould there be a big deal ? www.educatehealth.ca

  3. www.educatehealth.ca 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.

  4. www.educatehealth.ca 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.

  5. Case 1 Mrs W.S., LLM • 62 y/o obese lawyer with GERD • PMH: • Smoking 1ppd x 30 yrs • No HTN, No DM, No Cholesterol at her last visit in Jan 2010 Douen www.educatehealth.ca

  6. Case 1 Mrs W.S. • HPI • Speaking with niece regarding a legal matter when.. • Slurred speech  Loss of speech • Right facial droop, Right arm weak and incoordinated • EMS • Symptoms resolved with 15 min • Patient declines transfer to ER • Elects to way 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 www.educatehealth.ca

  7. Case Examination in office the next day: BP = 160/90 ; HR 90 and regular. No neurological deficits, but with right carotid Bruits. 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 ? www.educatehealth.ca

  8. Stroke Mimics Migraine (aura) Vertigo Syncope (vaso-vagal, cardiogenic, metabolic) Seizure (simple, CPSz, grand mal with “Todd’s”) Structural brain lesions (tumors, AVM, subdurals, abscess) Carpal tunnel (focal numbness) Radiculopathies (focal numb/weak) Neuropathies (more diffuse numb +/- weak) Dementia (confusion) Neuroses Stress/Anxiety Malingering www.educatehealth.ca

  9. 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 www.educatehealth.ca

  10. www.educatehealth.ca 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

  11. www.educatehealth.ca 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

  12. www.educatehealth.ca 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.

  13. www.educatehealth.ca Stroke patients: risk of recurrent event TIA patients: risk of recurrent event 20 18.5 20 17.3 15.0 15 15 11.5 11.5 TIA patients (%) 10 10 Stroke patients (%) 8.0 5 5 0 0 7-day stroke risk 30-day stroke risk 3-month stroke risk 30-day stroke risk 3-month stroke risk 7-day stroke risk Coull et al. BMJ 2004; 328: 326. Nearly 1 in 5 stroke/TIA patients is at risk of a recurrent event within 3 months

  14. The ABCD2 Score www.educatehealth.ca

  15. The ABCD2 Score www.educatehealth.ca 1 1 2 1 0 5

  16. www.educatehealth.ca Risk Factors for Stroke Within 90 Days of a TIA The ABCD2 Score High Risk Intermediate Risk Stroke Risk (%) Low Risk ABCD2 Score Lancet 2007;369:283-92.

  17. 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 www.educatehealth.ca

  18. www.educatehealth.ca Pathophysiology: Multiple Mechanisms requiring urgent W/U Antiplatelet (Anticoagulation) Douen

  19. 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 ? www.educatehealth.ca

  20. 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) www.educatehealth.ca

  21. www.educatehealth.ca 4. 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

  22. www.educatehealth.ca 4. 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

  23. 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 ? www.educatehealth.ca

  24. www.educatehealth.ca 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

  25. www.educatehealth.ca 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

  26. www.educatehealth.ca 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

  27. www.educatehealth.ca Timeliness of Care In Patients with TIAThe OXVASC Study Neurology 2005;65:371-5.

  28. www.educatehealth.ca The Consequences of Delaying Access to CareThe OXVASC Study Stroke Patients Neurology 2005;65:371-5.

  29. www.educatehealth.ca Timing of Surgical InterventionThe NASCET and ECST Studies 5 Year ARR In Stroke (%) 0-2 2-4 4-12 >12 Time From Event to Randomization (weeks) Lancet 2004;363:915-24.

  30. 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 ? www.educatehealth.ca

  31. www.educatehealth.ca 2. 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

  32. www.educatehealth.ca 2. 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

  33. www.educatehealth.ca Stroke / TIA Interventional Medical Revascularization CEA vs Stent Risk factor management Antithrombotic Antiplatelet Anticoagulant

  34. www.educatehealth.ca 5. In an ASA naive patient which of the following Antitrhomboticagents 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)

  35. www.educatehealth.ca 5. In an ASA naive patient which of the following Antitrhomboticagents 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)

  36. www.educatehealth.ca Prevention of Vascular Events in Stroke/TIA Patients with ASA Following First Stroke 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 ASA vs. Placebo: Efficacy by Dose* * 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.

  37. www.educatehealth.ca

  38. www.educatehealth.ca 6. For patients already on ASA which of the following Antitrhomboticagents 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)

  39. www.educatehealth.ca 6. For patients already on ASA which of the following Antitrhomboticagents 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)

  40. www.educatehealth.ca MATCH: Bleeding Complications Increased Significantly Clopidogrel + ASA (n=3,759) p<0·0001 Clopidogrel + Placebo (n=3,781) 120 (3%) 120 p<0·0001 96 (3%) 100 p<0·0001 73 (2%) 80 Number (n/%) with event 60 49 (1%) 39 (1%) 40 22 (1%) 20 0 Life-threatening bleeding Major bleeding Minor bleeding Diener et al. Lancet 2004; 364: 331–337.

  41. www.educatehealth.ca Major Bleeding 2.4 %/year RR = 1.06 P = 0.67 2.2 %/year CumulativeHazard Rates # at Risk C+A 33353172 2403914 OAC 3371 32122423 901 Years

  42. www.educatehealth.ca 7. For patients already on Plavix which of the following Antitrhomboticagents 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)

  43. www.educatehealth.ca 7. For patients already on Plavix which of the following Antitrhomboticagents 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)

  44. www.educatehealth.ca 8. In terms of the efficacy for non-cardioembolic prophylaxis which of the following are true: • ASA/ER Dipyridamole > ASA > warfarin • Clopidogrel >ASA > warfarin • Warfarin > Clopidogrel = ASA/ER Dipyridamole • Warfarin = ASA • Clopidogrel = ASA/ER Dipyridamole • D) and e) correct

  45. www.educatehealth.ca 8. In terms of the efficacy for non-cardioembolic prophylaxis which of the following are true: • ASA/ER Dipyridamole > ASA > warfarin • Clopidogrel >ASA > warfarin • Warfarin > Clopidogrel = ASA/ER Dipyridamole • Warfarin = ASA • Clopidogrel = ASA/ER Dipyridamole • d) and e) correct

  46. Secondary prevention- Which Antiplatelet ? Physician’s choice Compliance Cost www.educatehealth.ca

  47. 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 ?? www.educatehealth.ca

  48. 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 ?? www.educatehealth.ca

  49. Cardioemboli • AF: • High incidence of paroxysmal AF in acute stroke • 13.5% detection of new onset AF • 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 www.educatehealth.ca

  50. AF increases the risk of stroke www.educatehealth.ca • AF is associated with a pro-thrombotic state • ~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 CollCardiol2000;35:183-187; 4. Lin H-J, et al. Stroke 1996; 27:1760-1764; 5. Marini C, et al. Stroke 2005;36:1115-1119.

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