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  • 1. TIA: Opportunity for Prevention 2009 Cardiovascular Health Summit Nicholas J. Okon, D.O. Vascular Neurologist Billings, MT Portland, OR
  • 2. Overview • TIA represents ideal opportunity for preventing stroke • Very hi risk of stroke after TIA in first 48 hrs • ABCD2 score allows accurate prediction of risk • Time for a paradigm shift in the evaluation and treatment of TIA and minor stroke victims • Hi risk of future vascular events and vascular death in TIA and stroke patients • Future direction
  • 3. TIA: Opportunity for Prevention • Stroke is ideally suited for prevention • High prevalence • High economic cost • High burden of illness • Preventive measures are safe and efficacy has been validated Gorelick PB. Stroke 1994;25:220-224
  • 4. TIA: Opportunity for Prevention • TIA represents the best opportunity to intervene and prevent stroke. • Inconsistent approach to management in the ED throughout US • Recent refinement of short term-risk (48hr) allows for application of systematic approach
  • 5. TIA Public Health Burden • 4.9 Million people in the US report being diagnosed withTIA • An est. 2.3% US adults experience TIA • Many more recall symptoms consistent withTIA but did not seek medical attention Neurology SC Johnston 2003;60:1429-34
  • 6. Stroke Public Health Burden • Approximately 11% of patients diagnosed with TIA in the ED will have a stroke in 90 days • 15-20% of patients with stroke have a preceding TIA • 15-20% of patients with stroke have had a preceding minor stroke • Additional 4.9 Million people in the US report being diagnosed with stroke • Similar prevalence of stroke-2.3% US adults Neurology SC Johnston 2003;60:1429-34
  • 7. Knowledge of TIA • Only 8.2% of US adults able to identify correct definition of TIA • Only 8.6% of US adults able to recognize at least one common symptom of TIA • Older age, lower income and fewer years of education predict TIA and stroke Neurology SC Johnston 2003;60:1429-34
  • 8. Case: Mr. JM • 68 y/o male smoker with recently diagnosed HTN presents to local ED with 20 minutes right hemiparesis and speech changes 4 hours ago.
  • 9. Case:Mr. JM • Incomplete history taken by ED provider • BP 150/90 • NL limited neurologic exam • CT head read as normal • No contact with Neurologist • Patient discharged from ED with instructions to follow up with Primary provider +/- Aspirin
  • 10. Case:Mr. JM • What’s Mr. JM’s diagnosis? TIA or Minor stroke? • What is his risk of stroke after this event? • What other testing should be performed and when? • What is the best method for prevention?
  • 11. How is TIA defined? • Classic definition of TIA: • sudden, focal neurologic deficit lasting < 24 hrs. • presumed to be of vascular origin • confined to an area of the brain or eye perfused by a specific artery
  • 12. Problems with classic definition of TIA • presumes that if symptoms resolve completely then no permanent ischemic damage has occurred suggesting that TIAs are benign • 24 hr criterion is arbitrary and assumes that if symptoms last >24 hrs an injury to brain parenchyma should be detectable by microscopy • numerous studies have shown (since 1958) that the majority of TIAs last < 1 hour
  • 13. New Definition of TIA • “ATIA is a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction” The TIA Working Group N Engl J Med 2002;30(11):2502
  • 14. New Definition of TIA: further clarification • “Patients who have transient focal symptoms of brain ischemia -- and who, on diagnostic evaluation, are found to have an acute infarction-- would no longer be classified as having a TIA, regardless of the duration of clinical symptoms.” The TIA Working Group N Engl J Med 2002;30(11):2502
  • 15. Case:Mr. JM • What’s Mr. JM’s diagnosis? TIA or Minor stroke? --TIA. • What is his risk of stroke after this event? • What other testing should be performed and when? • What is the best method for prevention?
  • 16. Risk of stroke after TIA
  • 17. Long-Term Risk of Stroke: Percentage of Patients Experiencing Stroke Feinberg WM, Albers GW, Barnet HJM, et al. Stroke 1994;25(6):1320-35. Sacco RL. Neurology 1997;49(Suppl 4):S39-S44. Sacco RL, Shi T, Zamanillo MC, et al. Neurology 1994;44:626-34. Broderick J, Brott T, Kothari R, et al. Stroke 1998;29:415-21. After TIA After Stroke 30 days 4-8% 3-10% 1 year 12-13% 10-14% 5 years 24-29% 25-40%
  • 18. Short-term prognosis after ED diagnosis of TIA • 1707 patients diagnosed with TIA by ED docs • 99% presented in 24 hrs • 50% had symptoms upon arrival to ED • 21% of strokes were fatal: 64% were disabling SC Johnston JAMA 2000;284:2901-2906
  • 19. 1707 patients identified by ED docs withTIA among 16 hospital in HMO in northern California. SC Johnston JAMA 2000;284:2901-2906
  • 20. 90 Day Risk of Stroke After TIA Increases with Number of Risk Factors Risk Factors Age > 60 y Diabetes Symptoms > 10 min Weakness Speech Impairment SC Johnston JAMA 2000;284:2901-2906
  • 21. ABCD score • Score derived for 7-day risk of stroke in population-based cohort of patients with TIA (Oxfordshire CommunityStroke Project) • Further validated in the OxfordVascular Study • 6-point clinical-based score proved highly predictive of 7 day risk of stroke Rothwell,PM Lancet 2005 Jul 2-8;366(9479):29-36
  • 22. ABCD score Rothwell,PM Lancet 2005 Jul 2-8;366(9479):29-36
  • 23. ABCD score Rothwell,PM Lancet 2005 Jul 2-8;366(9479):29-36
  • 24. ABCD2 score Johnston SC, Rothwell,PM Lancet 2007 Jan 27;369(9558):283-92
  • 25. ABCD2 score • Age > 60 years 1 pt. • BP > 140/90 or DBP > 90 1 pt. • Clinical: • Focal/Unilateral Weakness or 2 pt. • Speech impairment 1 pt. • Duration of Symptoms: • > 60 minutes or 2 pt. • 10-59 minutes 1 pt. • Diabetes Mellitus 1 pt. Johnston SC, Rothwell,PM Lancet 2007 Jan 27;369(9558):283-92
  • 26. ABCD2 score Johnston SC, Rothwell,PM Lancet 2007 Jan 27;369(9558):283-92
  • 27. ABCD2 score • Age > 60 years (1 pt.) 1 • BP > 140/90 or DBP > 90 (1 pt.) 1 • Clinical: • Focal/Unilateral Weakness or (2 pt.) 2 • Speech impairment (1 pt.) • Duration of Symptoms: • > 60 minutes or (2 pts.) • 10-59 minutes (1 pt.) 1 • Diabetes Mellitus (1 pt.) 0 • Total 5
  • 28. Case:Mr. JM • What’s Mr. JM’s diagnosis? TIA or Minor stroke? --TIA. • What is his risk of stroke after this event? >4% in 48hrs • What other testing should be performed and when? • What is the best method for prevention?
  • 29. Risk of stroke after TIA also dependent on cause Lovett, JK (Oxfordshire) Neurology 2004;62:569-74
  • 30. Nearly half of highest 90 day risk occurs in first 48hrs --5.5%) 48 hrs 48 hrs
  • 31. Case:Mr. JM • What’s Mr. JM’s diagnosis? TIA or Minor stroke? --TIA. • What is his risk of stroke after this event? >4% in 48hrs • What other testing should be performed and when? Labs (cholesterol,FBG,CBC), Brain MRI and head and neck vascular imaging (MRA,CTA,US) and echocardiography (TTE+/-TEE) <48 hrs. • What is the best method for prevention?
  • 32. Time for a paradigm shift in the evaluation and treatment of TIA and minor stroke victims
  • 33. Effect of urgent treatment of transient ischemic attack and minor stroke on early recurrent stroke (EXPRESS study) • Population-based study of pre (Phase 1) and post (Phase 2) implementation of urgent assessment and immediate treatment in clinic in patients with TIA and minor stroke not admitted to hospital • Phase 1; PCPs made referral, visit then scheduled by specialty clinic and recommendations faxed back to PCP after evaluation • Phase 2; PCPs sent patients directly to specialty clinic after presentation without referral or appointment and treatment initiated in the specialty clinic Rothwell, PM Lancet 2007;370 (9596):1432-1442
  • 34. • Median delay to clinic assessment fell from 3 to 1 day • Median delay to first prescription fell from 20 to 1 day • 80% reduction in 90 day risk of early recurrent stroke Effect of urgent treatment of transient ischemic attack and minor stroke on early recurrent stroke (EXPRESS study) Rothwell, PM Lancet 2007;370 (9596):1432-1442
  • 35. A transient ischemic attack clinic with round- the-clock access (SOS-TIA): feasibility and effects • 1085 TIA patients calling toll-free phone # then seen at hospital clinic with 24 hr access in Paris,France • 53% seen <24 hrs from symptom onset • 65% with TIA or minor stroke • Standard assessment <4 hrs after admission • 87% seen by vascular neurologist <24 hrs from phone call • 90 day and 1 yr outcomes compared to ABCD2 predicted outcome Lancet Neurol 2007;9:953-60
  • 36. • 26% admitted to stroke unit, 76% D/C’d same-day of evaluation • 95% had brain, arterial and cardiac imaging • Cause identified in 41% of those with normal brain imaging; 64% with minor stroke; 74% with TIA and abnormal brain imaging • All patients received 300-500mg ASA • Goals for secondary prevention faxed to PCP after direct communication by phone and before d/c A transient ischemic attack clinic with round- the-clock access (SOS-TIA): feasibility and effects Lancet Neurol 2007;9:953-60
  • 37. • Antithrombotics given immediately in 98% • BP meds started or modified in 24% • Lipid lowering therapy started or modified in 45% • >75% patients with atrial fibrillation received anticoagulants • 5% needed carotid revascularization and received it < 6 days form initial evaluation A transient ischemic attack clinic with round-the- clock access (SOS-TIA): feasibility and effects Lancet Neurol 2007;9:953-60
  • 38. • 90 day stroke rate 1.24% vs. 5.96% ABCD2 predicted • 1 year rate of MI and vascular death 50% less than reported meta-analysis (1.1% vs. 2.2%) A transient ischemic attack clinic with round- the-clock access (SOS-TIA): feasibility and effects Lancet Neurol 2007;9:953-60
  • 39. Hi risk of future vascular events and vascular death in TIA and stroke patients
  • 40. Risk of Myocardial Infarction andVascular Death After Transient Ischemic Attack and Ischemic Stroke A Systematic Review and Meta-Analysis • Meta-analysis of 39 studies including 66,000 patients with mean follow up of 3.5 years • 2.1% annual risk of nonstroke vascular death • 2.2% annual risk of total MI (fatal and non) Touze,E Stroke 2005;36:2748
  • 41. Long-term survival and vascular event risk after TIA or minor stroke: LiLAC (Life Long After Cerebral ischemia) Study • 10 yr follow-up of Dutch TIA Trial • 2473TIA or minor strokes < 3 month randomized to ASA 30mg or 283 from 1986-89 • cardio-embolic and clotting disorders excluded • TIA defined as <24 hrs Lancet 2005;365:2098-104
  • 42. • 60% died of vascular causes at 10 yrs. • 54% experienced at least 1 new vascular event • Event-free survival 48% at 10 years Long-term survival and vascular event risk after TIA or minor stroke: LiLAC (Life Long After Cerebral ischemia) Study Lancet 2005;365:2098-104
  • 43. Long-term survival and vascular event risk after TIA or minor stroke: LiLAC (Life Long After Cerebral ischemia) Study Lancet 2005;365:2098-104
  • 44. • Strongest predictors of all cause death: • Age> 65 • Diabetes • Hx claudication or prior PVD surgery • Abnormal baseline ECG Long-term survival and vascular event risk after TIA or minor stroke: LiLAC (Life Long After Cerebral ischemia) Study Lancet 2005;365:2098-104
  • 45. Case:Mr. JM • What’s Mr. JM’s diagnosis? TIA or Minor stroke? --TIA. • What is his risk of stroke after this event? >4% in 48hrs • What other testing should be performed and when? Labs (cholesterol,FBG,CBC), Brain MRI and head and neck vascular imaging (MRA,CTA,US) and echocardiography (TTE+/-TEE) <48 hrs. Lower extremity arterial doppler. • What is the best method for prevention?
  • 46. Future Direction Combining multiple therapeutic strategies for secondary prevention
  • 47. Combining Multiple Approaches for the Secondary Prevention ofVascular Events After Stroke • Quantitative modeling study using published meta-analyses of RCTs of secondary prevention and hi-risk primary prevention of vascular events • Baseline rates of vascular events taken from LiLAC study • Calculated cumulative relative risk and absolute risk reductions assuming a multiplicative scale • Used 5 risk-reducing strategies with the broadest applicability to patients with stroke and TIA: dietary modification, exercise, aspirin, statins and antihypertensive therapy Stroke 2007;38:1881-1885
  • 48. Calculated cumulative risk reduction for implementing diet, exercise, aspirin, statins, and antihypertensive therapy ARR 20% NNT=5 ARR 35% NNT=3 82% 80% Stroke 2007;38:1881-1885
  • 49. • Combining 5 key strategies reduces the risk of recurrent vascular events by > 80% in patients with history of TIA or stroke. • Only 5 patients need to be treated to prevent 1 major vascular event over 5 years. • Intensified management with ASA+ER dipyridamole, intensive BP lowering and hi-dose statins lead to > 90% cumulative risk reduction. Stroke 2007;38:1881-1885 Combining Multiple Approaches for the Secondary Prevention of Vascular Events After Stroke
  • 50. Case:Mr. JM • What’s Mr. JM’s diagnosis? TIA or Minor stroke? --TIA. • What is his risk of stroke after this event? >4% in 48hrs • What other testing should be performed and when? Vascular imaging <48 hrs. • What is the best method for prevention? Combination medical therapy with exercise and dietary modification
  • 51. Summary • Hi short-term risk of stroke after TIA requires urgent and expedient evaluation and immediate initiation of secondary prevention therapies • Specialized 24-hr appointment-less access clinics superior to current standard practice • Hi risk of vascular events and vascular death in TIA and minor stroke patients demands expanding scope of evaluation to include additional vascular beds • Multimodal/combination drug therapy with exercise and diet modification holds promise of substantial risk reduction