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Transient Ischemic Attack Patient Update: The Optimal Management of Emergency Department Patients With Suspected Cereb

Transient Ischemic Attack Patient Update: The Optimal Management of Emergency Department Patients With Suspected Cerebral Ischemia. Rapid TIA Patient Evaluation and Treatment: Lessons Learned from FASTER, EXPRESS, and SOS-TIA. TIA – is it an emergency?.

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Transient Ischemic Attack Patient Update: The Optimal Management of Emergency Department Patients With Suspected Cereb

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  1. Transient Ischemic Attack Patient Update: The Optimal Management of Emergency Department Patients With Suspected Cerebral Ischemia

  2. Rapid TIA Patient Evaluation and Treatment: Lessons Learned from FASTER, EXPRESS, and SOS-TIA

  3. TIA –is it an emergency? What is the optimal management of ED patients with suspected cerebral ischemia?

  4. Jonathan A. Edlow, MDVice-chairmanDepartment of Emergency MedicineBeth Israel Deaconess Medical CenterAssociate Professor of MedicineHarvard Medical SchoolBoston, MA

  5. Disclosures • Dr. Edlow is a member of the ACEP Clinical Policies committee

  6. Session Objectives • Evaluate which therapies might be initiated for ED TIA patients in order to minimize the subsequent stroke risk and maximize patient outcome.

  7. Treatment • Should I start an anti-platelet drug? If so, which one? • Is there a significant carotid stenosis? How is this best treated? • Is there atrial fibrillation or other cardio-embolic sources of the TIA?

  8. Anti-platelet therapyAHA guidelines - 2006 • ASA – dose 50-325mg • ASA plus extended release dipyridamole (50-400mg) • Clopidogrel (75mg)

  9. CASTIA (on-going) Clopidogrel + ASA v Clopidogrel <24h Early ASA v placebo studies CAPRIE (1996) ASA v Clopidogrel MATCH (2006) Clopidogrel + ASA v Clopidogrel alone FASTER (2007) <24h Clopidogrel + ASA v ASA (and simvastatin v placebo) ESPS-2 (1996) ASA v ASA-dipyridamole PRoFESS (on-going) ASA-Dipyridamole v clopidogrel (and telmisartan v placebo) ESPRIT (2007) ASA v ASA- dipyridamole CHARISMA (2006) Clopidogrel + ASA v ASA alone

  10. ASA • High dose no more effective than low dose • More side effects (bleeding) with high dose • 20-25% RRR (compared to placebo) • High quality evidence

  11. ASA v ASA+dipyridamole • ESPS-2 (1996) • ESPRIT (2006) • Verro (2008) meta-analysis of these studies plus several smaller ones • Better results with extended release • ~ 6% dropped out due to HA

  12. Clopidogrel v ASA • CAPRIE (1996) • > 19,000 patients, clopidogrel 75 vs ASA 325 daily, f/u 1-3 years • ARR of 0.51, RRR of 8.7% (favors clopidogrel) • Safety equivalent

  13. Clopidogrel-ASA v either alone • CHARISMA - (C75 + ASA) v ASA • MATCH - (ASA75 + C75) v C75 • FASTER – (ASA + C300/75) v ASA (and simvastatin v placebo) • PRoFESS – (ASA + Di) v C (Telmisartan v placebo), a study that will enroll 20,000 patients, 8,000 within the first 7 days) C = clopidogrel ASA = aspirin Di = dipyridamole

  14. MATCH double-blinded placebo-controlled trial • 7599 patients with recent ischemic stroke or TIA + 1 additional vascular risk factor • Aspirin + clopidogrel v clopidogrel alone • Primary endpoint: composite ischemic stroke, MI, vascular death, or re-hospitalization for acute ischemia (including for TIA, angina, or worsening PVD) • ARR for primary endpoint: 1% • ARI for life-threatening bleeds: 1.3% MATCH; Diener HC et al; Lancet 2004; 364: 331-337.

  15. MATCHEfficacy Safety

  16. MATCH trial patient characteristics

  17. FASTERrandomized 2x2 factorial design • 392 patients enrolled < 24hours from index event • Aspirin + clopidogrel v aspirin alone • Primary endpoint: total 90-day stroke • 7.1% with clopidogrel and aspirin • 10.8% with aspirin alone • (ARR: 3.7%, 95% CI −9.4 to 1.9, p=0·19) • 2 patients in the clopidogrel arm had ICH versus 0 in the placebo (aspirin only) arm (NS) FASTER; Kennedy, G; Lancet Neurology; 2007.

  18. FASTER v MATCH • Enrollment time window • FASTER ≤ 24 hours • MATCH < 3 months • Proportion of patients with LAA v small vessel disease • Both required AIS or TIA as qualifying event but MATCH required 1 additional risk factor • What’s being compared? • FASTER: Clopidogrel + aspirin v aspirin • MATCH: Clopidogrel + aspirin v clopidogrel

  19. Stroke Risk Depends on the Location of the Disease Rothwell PM et al. Lancet Neurology 2006;5:323–31.

  20. Anti-platelet therapyEarly intervention trials • Except for FASTER, only 2 other trials have enrolled patients “early” • IST and CAST showed a reduced recurrence of stroke and/or death in the near term (14d in IST and 30d in CAST) • ARR of about 1% when ASA given in the first 48 hrs CAST; Lancet 1997;349:1641–1649 IST; Lancet 1997; 349: 1569-1581

  21. Supporting evidence that clopidogrel + ASA helps? • EXPRESS • SOS-TIA Rothwell PM et al. Lancet 2007;370:1432-1442. Lavellee PC et al. Lancet Neurology; 2007;6:953-960.

  22. EXPRESS • Before v After method • Phase 1 (4-1-02 to 9-30-04) treatment initiated in Primary Care with appointment required to TIA clinic • Phase 2 (10-1-04 to 3-31-07) treatment initiated in TIA clinic, no appointment necessary • Nested in ongoing Oxford Vascular Study so other factors same; “before” group prospectively collected data

  23. EXPRESS • Phase 1 – 634 pts -> 310 to EXPRESS • Phase 2 – 644 pts -> 281 to EXPRESS (Other patients went directly to ED or hospital) • Baseline characteristics similar • Time to Rx – 20 days to 1 day • 90 day stroke rate – 10.3% to 2.1%

  24. EXPRESS

  25. EXPRESS

  26. EXPRESS

  27. SOS-TIA • 24 hour access hospital-based clinic for TIA patients • Assessment began ≤ 4 hours • 1-3-03 to 12-31-05, 1085 patients admitted to the clinic • Median symptom duration : 15 minutes • 53% seen ≤ 24 hours of symptom onset

  28. SOS-TIA 787 patients with definite or possible TIA

  29. SOS-TIA outcomes

  30. SOS-TIA outcomesPatients with confirmed or possible TIA • All started a stroke prevention program • 824/845 (98%) got “anti-thrombotic” meds • 43 (5%) had urgent carotid revascularization (median delay 6 days) • 44 (5%) were anticoagulated for Afib • 808 (74%) were sent home same day

  31. CEA – Faster is better For patients with ≥ 50% stenosis, the NNT to prevent 1 ipsilateral ischemic stroke was: CEA ≤ 2 weeks – 5 CEA > 12 weeks – 125 Rothwell; Lancet March 20, 2004

  32. AFib and other cardioembolic sources • Full anti-coagulation • A heparin followed up by an oral anti-coagulant

  33. Anti-platelet agents • AHA 1st line – ASA, ASA-dipyridamole or clopidogrel • ASA failure • no evidence that increasing dose helps • no evidence to switch to warfarin • ASA intolerance – use clopidogrel • Individualize

  34. Individualizing therapy • Cost • Side effects • Other co-morbidities (eg, CAD needing stent) • PRoFESS, CASTIA may give us more answers soon regarding ASA-dipyridamole v clopidogrel • Clopidogrel + ASA may work, if started early and stopped after a few months

  35. TIA in the ED – big picture • We are there 24x7 • We can begin most of the interventions • Emergency Medicine is well placed to prevent strokes in these patients

  36. Questions?www.ferne.orgjedlow@bidmc.harvard.edu ferne_clindec_2008_tia_edlow_clintrials_extended_062508_final

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