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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 Cerebral Ischemia

rapid tia patient evaluation and treatment lessons learned from faster express and sos tia

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

tia is it an emergency
TIA –is it an emergency?

What is the optimal management of ED patients with suspected cerebral ischemia?

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

disclosures
Disclosures
  • Dr. Edlow is a member of the ACEP Clinical Policies committee
session objectives
Session Objectives
  • Evaluate which therapies might be initiated for ED TIA patients in order to minimize the subsequent stroke risk and maximize patient outcome.
treatment
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?
anti platelet therapy aha guidelines 2006
Anti-platelet therapyAHA guidelines - 2006
  • ASA – dose 50-325mg
  • ASA plus extended release dipyridamole (50-400mg)
  • Clopidogrel (75mg)
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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

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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
asa v asa dipyridamole
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
clopidogrel v asa
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
clopidogrel asa v either alone
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

match double blinded placebo controlled trial
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.

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MATCH trial

patient characteristics

faster randomized 2x2 factorial design
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.

faster v match
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
stroke risk depends on the location of the disease
Stroke Risk Depends on the Location of the Disease

Rothwell PM et al. Lancet Neurology 2006;5:323–31.

anti platelet therapy early intervention trials
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

supporting evidence that clopidogrel asa helps
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.

express
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
express1
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%
sos tia
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
sos tia1
SOS-TIA

787 patients with definite or possible TIA

sos tia outcomes patients with confirmed or possible tia
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
cea faster is better
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

afib and other cardioembolic sources
AFib and other cardioembolic sources
  • Full anti-coagulation
  • A heparin followed up by an oral anti-coagulant
anti platelet agents
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
individualizing therapy
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
tia in the ed big picture
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
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Questions?www.ferne.orgjedlow@bidmc.harvard.edu

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