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BRAIN ATTACK

BRAIN ATTACK. ADVANCES IN SECONDARY STROKE PREVENTION. Dr. Toni Winder November 2007. Advances in Secondary Stroke Prevention. Learning Objectives : Upon completion of this session, participants will be able to: Describe 4 components of secondary stroke prevention

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BRAIN ATTACK

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  1. BRAIN ATTACK ADVANCES IN SECONDARY STROKE PREVENTION Dr. Toni Winder November 2007

  2. Advances in Secondary Stroke Prevention Learning Objectives: Upon completion of this session, participants will be able to: • Describe 4 components of secondary stroke prevention • Identify TIA / Stroke patients requiring urgent secondary stroke prevention interventions • Explain strategies to reduce risk of recurrent stroke

  3. Epidemiology of Stroke: The Canadian Perspective • 50,000 new stroke patients/year in Canada† • 300,000 stroke survivors† • 4th leading cause of death in Canada • The leading cause of adult disability • 28% of stroke patients are under age 65* Heart and Stroke Foundation of Alberta, NWT and Nunavut 2007

  4. Lacunar 20% Thromboembolic 10% SAH 10% Cardioembolic 20% Hemorrhagic 20% Ischemic 80% ICH 10% Unknown 25% Other 5% Stroke Subtypes Adapted from Foulkes MA, et al. Stroke 1988;19:547-554

  5. Outcome of Ischemic Stroke Heart and Stroke Foundation of Alberta, NWT and Nunavut 2007

  6. Second Strokes • Stroke or TIA survivors have an increased risk of a subsequent stroke • Recurrent strokes are more likely than initial strokes to result in disability and death • ~ 20%-40% of strokes are preceded by a TIA or non disabling stroke (Rothwell et al. Lancet Neurol 2006; 5: 323-331) Golden Opportunity for Stroke Prevention!

  7. Risk of Vascular Events After Stroke or TIA MI 14 stroke 12 10 8 Patients with events (%) 6 4 2 0 CATS TASS CAPRIE ESPS-2 CATS = Canadian American Ticlopidine Study TASS = Ticlopidine Aspirin Stroke Study CAPRIE = Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events ESPS-2 = European Stroke Prevention Study 2 Adapted from Albers GW Neurlogy 2000;54:1022-1028

  8. TIA vs. Stroke TIA = threatened stroke - “Angina” of the brain Conventional Definition: • TIA: neurological symptoms lasting < 24 hours Tissue Based Definition of TIA: Modern technology • Rapidly resolving neurological symptoms, typically lasting < 1 hr, with no evidence of infarction on MRI 40 - 60% of TIAs associated with an area of infarction on MRI

  9. TIA Stroke Risk Risk of stroke following TIA is high: • 10-20% within 90 days • 50% of these within the first 2 days (48 hours) Johnston et al. JAMA 2000; 284: 2901-06 EARLY PREVENTION STRATEGIES can make a difference! ACT FAST!

  10. Approach to Secondary Stroke Prevention Based on: Cause of Event Existing Stroke Risk Factors

  11. Components of Secondary Stroke Prevention • Evaluate the Event • Implement Interventions • Initiate Medications • Modify Stroke Risk Factor

  12. Evaluate the Event

  13. Evaluate the Event • TIA/Minor Stroke Risk Assessment • Clinical Predictors • Investigations • CT, MRI, ECG, Carotid imaging, echocardiogram

  14. Evaluate the Event: TIA / Minor Stroke Risk Assessment ABCD Score: Predict 7 day stroke risk; Identified 4 areas associated with high risk Points • Age ≥ 60 1 • Blood pressure ≥ 140/90 1 • Clinical features • Unilateral weakness 2 • Speech disturbance without weakness 1 • Duration of symptoms • > 10 min < 59 min 1 • ≥ 60 min 2 Risk: Score < 5 = 0.4% risk; Score of 5 = 16% risk; Score of 6 = 35% risk Rothwell et al. Lancet; 2005; 366: 29-36

  15. ABCD2 ScoreRothwell et al. Lancet; 2007; 369: 283-292

  16. Evaluate the Event: TIA / Minor Stroke Risk Assessment TIA Stroke Risk Assessment Low Risk • System onset > 48 hours with ABCD2 score < 5 • Pure sensory deficit • Pure ataxia Medium Risk • Symptom onset > 48 hours with ABCD2 score ≥ 5 • Symptom onset < 48 hours with ABCD2 score < 5 High Risk • Symptom onset < 48 hours with ABCD2 score ≥ 5

  17. Evaluate the Event: Investigations • Labs - CBC, lytes, Cr, gluc, PTT, INR, fasting lipids • ECG • ? Cardiac cause - afib • Holter monitor • CT or MRI • Rule out mimics, identify stroke type • Carotid Imaging (carotid dopplar, CTA or MRA) • Identify stenosis • Echocardiogram • If suspect cardiac cause

  18. IMPLEMENT INTERVENTIONS ACT FAST WITH HIGH RISK PATIENTS!

  19. SOS - TIA

  20. Implement Interventions: Carotid Endarterectomy If TIA due to ≥ 50% stenosis in extracranial carotid artery consider CEA Greatest benefit it surgery within 2 weeks Rothwell et al. Lancet; 2004; 363: 915-25

  21. Early Carotid Surgery Better in 50-69% stenosis NNT 7 Rothwell PM et al. Stroke 2004;35:2855-2861.

  22. Early Carotid Surgery Much Better >70% w/o near-occlusion Rothwell PM et al. Stroke 2004;35:2855-2861. NNT 3

  23. Implement Interventions: TIA / Minor Stroke Rapid assessment of all events: Initiate antithrombotic therapy Low Risk • CT and Carotid investigations within 1-2 weeks • Stroke Prevention Clinic Referral Medium Risk • CT and Carotid Investigations ASAP (within 72 hours) • Semi Urgent Stroke Prevention Clinic Follow-up (within 1 week) High Risk • Urgent CT and Carotid Investigations (ASAP-within 24 hr, while in ER or admit) • > 50% ICA stenosis - Contact Comp. Stroke Center- transfer for possible CAE • ≤ 50% ICA stenosis - Discharge unless high suspicion cardiac course (echocardiogram) • Stroke Prevention Clinic Referral

  24. INITIATE MEDICATIONS

  25. Initiate Medications: Antithrombotic Therapy • Thrombotic mechanisms are present in most ischemic strokes • Antithrombotic therapy reduces risk • This is the only therapy/ treatment that immediately reduces stroke risk

  26. Initiate Medications: Antithrombotic Therapy Aspirin (50-325 mg/day) is first line treatment • If aspirin naïve- load with 160mg then 81 mg OD Options: Aspirin/extended release dypridamal (Aggrenox) • 25mg/200mg OD Clopidogrel (Plavix) • 75 mg OD, consider loading with 300 mg Aspirin + Clopidogrel • ASA 81mg OD + Clopidogrel 75mg OD • Consider loading dose of each agent • May use with High Risk TIA/Minor Stroke • Short term use - no longer than 1 month

  27. Initiate Medications: Antithrombotic Therapy If cardioembolic source: • Long-term anticoagulation (Warfarin) • Target INR 2.0 - 2.5

  28. MODIFY RISK FACTORS

  29. Medical conditions Hypertension Diabetes mellitus Hypercholesterolemia Obesity Insulin resistance? Cardiac diseases Atrial fibrillation Coronary artery disease CHF Behaviours Cigarette smoking Heavy alcohol use Physical inactivity Modifiable Stroke Risk Factors

  30. Treating Hypertension to Prevent Stroke • HTN is the single most important modifiable risk factor for stroke • HTN contributes to 70% of all strokes • Atheroma in carotids, aortic arch • Friability of small cerebral end arteries • LV dysfunction and atrial fibrillation

  31. Benefits of Treating Hypertension • Younger than 60 yrs • Reduces the risk of stroke by 42% • Reduces the risk of coronary event by 14% • Older than 60yrs • Reduces overall mortality by 20% • Reduces cardiovascular mortality by 33% • Reduces incidence of stroke by 40% • Reduces coronary artery disease by 15%

  32. Treat Hypertension Aggressively • Target most patients still < 140/90 • Home Measurement < 135/85 • Diabetics < 130/80 • Lifestyle Modification: • Sodium restriction, DASH diet, physical activity, weight loss, alcohol restriction, smoking cessation • Expect to use combination therapy • ACE inhibitor, ARB, diuretic

  33. PROGRESS TRIAL • Randomised placebo-controlled trial designed to determine the effects of a blood pressure-lowering regimen on the risks of stroke and other major vascular events in hypertensive and non hypertensive patients with a history of stroke or TIA Reference: Lancet 2001; 358: 1033-41

  34. PROGRESS TRIAL STROKE RISK REDUCTION 0.20 28% risk reduction 95% CI 17 - 38% p<0.0001 0.15 Placebo Active* Proportion with event 0.10 0.05 0.00 0 1 2 3 4 Follow-up time (years) *Active: perindopril 4 mg ± indapamide Reference: Lancet 2001; 358: 1033-41

  35. Hypertension: ACE Studies • HOPE (Heart Outcomes Prevention Evaluation) • Randomized controlled trial • Treatment - Ramapril 10 mg • Results - 30% relative risk reduction for stroke N Engl J Med 2000;342:145-153

  36. Hypertension: ARB Studies • LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) • Randomized controlled trial • Treatment: • Losartan + Atenelol placebo vs Atenelol + Losartan placebo • Hydrochlorothiazide added at 2 months • At 4 months - Losarten or Atenelol doubled to achieve target BP < 140/90 • Results • More patients reached target BP with Losarten vs Atenelol arm • 25% decrease incidence of diabetes • Less incidence of stroke, MI and death in Losarten arm Lancet 2002;359:995-1003

  37. Hypertension: ARB Studies • ACCESS (Acute Candesartan Cilexetil Evaluation in Stroke Survivors) • Patients with acute stroke and hypertension • Evaluate immediate BP reduction in acute stroke and severe hypertension • Randomized clinical trial • Treatment: • Candesartan 4-16mg/day x 7 days then continue for 1 year • Candesartan placebo x 7 days then candesartan 4-16mg for 1 year • Results - Candesartan in the first 7 days prevents cardiovascular morbidity and mortality at 1 year Stroke 2003;34:1699-1703

  38. Treatment of Hypertensionwith Cerebrovascular Disease • Strongly consider blood pressure reduction in all patients after the acute phase of non disabling stroke or TIA • Recommended agents: ACE-I, diuretics ARB - ongoing studies ß-blockers, CCB

  39. Hypercholesterolemia: Using Statins for Secondary Prevention of Stroke • Lipid-lowering trials using statins have shown benefit in decreasing progression and/or inducing regression of carotid artery plaque • Lipid-lowering trials using statins for secondary prevention (of CHD) have shown benefit in stroke prevention

  40. Why Should Statins Prevent Ischemic Stroke? • Lipid effects = LDL lowering • Target LDL-C < 2.0 mmol/L • Non-lipid effects = • Stabilizing plaques • Improving endothelial function • Decreasing inflammation • Decreasing platelet aggregation • Directly lowering blood pressure • Decreasing cardiac emboli

  41. Statin Studies • SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) • Double Blind Randomized Controlled Trial • Stroke or TIA within 1-6 months • Treatment: • Atorvastatin (Lipitor) 80 mg once daily or placebo • Results • 5 year absolute reduction in risk of stroke - 22% • 5 year absolute reduction in risk of major CV events - 3.5% • Significant increase in hemorrhagic stroke N Engl J Med 2006;355:549-559

  42. Hypercholesterolemia: Using Statins for Secondary Prevention of Stroke • Should statins be used if lipids normal? consider statin if event presumed to be of atherosclerotic origin even if no preexisting indications Stroke 2006;37:577-617

  43. Lifestyle: Weight Loss • Healthy BMI: 18.5-24.9 kg/m2 • Waist circumference:(CRESCENDO) <102 cm for men, <88 cm for women • ? Insulin Resistance (metabolic syndrome)

  44. Stroke Prevention Clinics • Evaluate, treat and educate to promote stroke risk reduction • Specialize in Secondary Stroke Prevention Strategies • Requires prompt / efficient referral process • Integration with lifestyle modification programs • Chronic disease management • Healthy lifestyle

  45. Secondary Stroke Prevention Evaluate the Event: Identify Events requiring Urgent intervention / Identify cause • TIA / Minor Stroke Risk Assessment • Investigations • CT, MRI, ECG, Carotid imaging, echocardiogram Implement Interventions • Carotid Endarterectomy Initiate Medications • Antiplatelets /anticoagulants, ACE-I, Diuretics, ARB, statins Modify Stroke Risk Factors • Vascular Risk Factors • Behavioral/Lifestyle Risk Factors

  46. BRAIN ATTACK STROKE CAN BE PREVENTED!

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