We see patients with ischemic strokes pretty frequently as Internists. We will use today’s journal club to go over some basics of acute ischemic stroke management, and the studies behind our management.

We went over CHANCE, POINT, SPARCL, FLAME, and FOCUS in detail, but the hyperlink to the other trials we briefly mentioned are included!

Acute Stroke Management

• ABC: Airway, breathing circulation
• History, physical, glucose, O2 sat, EKG, noncon head CT ASAP
• Determining time last see normal to see if patient is a candidate for tPA
  • 3-4.5 hours
  • Mechanical thrombectomy can be considered 16-24 hours (DAWN, DEFUSE 3)
• Additional studies as needed depending on pre-test probability
  • TTE, carotid US, etc if needed
• Things to consider in the acute setting
  • Fluids:
    • Ensure euvolemic, hypovolemic esp in older adults can worsen cerebral blood flow.
  • Hypoglycemia:
    • Severe hypoglycemia can cause neuronal injury, rapidly correct any hypoglycemic state
  • Hyperglycemia:
    • Associated with poor outcome in stroke patients. AHA/ASA guidelines aim for BG 140-180mg/dL
    • SHINE trial: tight glycemic control vs standard of care, no different in outcome
  • Swallow: Dysphagia screen prior to giving oral meds or food, aspiration precautions.
  • Head and body position:
    • Elevated head of the bed to 30 degrees if concerned for elevated intracranial pressure like is ICH, cerebral edema from large ischemic infarction, aspiration, or cardiac/pulm disease
  • Mobilization:
    • Do so after 24 hours after, dec risk of PNA, DVT, PE, pressure sores. Very early < 24 hours mobilization is associated with dec favorable outcome at 3 months (AVERT trial)
  • Fever:
    • Rule out infectious etiology
    • Can be present after brain injury, fever within 24 hours is associated with 2x inc in mortality at one month.
  • Blood pressure
    • Ischemic stroke only
      • Stabilize blood pressure below 180/105 for at least 24 hours if s/p tPA
      • If no tPA, permissive HTN, do not treat the BP unless SBP > 220 or DBP > 120, or if pt has underlying CAD, HF, aortic dissection, hypertensive emergency.
        • Lower BP by no more than 15% in the first 24 hours
        • Rate of blood pressure control will be dependent on vascular imaging, if a large artery stenosis is found, keep BP high to maintain cerebral blood flow.
        • Choice of meds: IV preferred, titratable, precise
          • Labetalol
          • Nicardipine
          • 2^nd line: Nitroprusside, inc risk of inc ICP, inc risk of stroke in older folks
      • Secondary prevention
        • Treat any modifiable risk factors
        • DAPT
        • Statin
        • BP control
        • Life style changes
        • Fluoxetine? (FLAME is favorable, FOCUS is not)

DAPT After Stroke

• CHANCE
  • Population
    • 5170 Chinese patients with high risk TIA or minor ischemic stroke within 24 hours of sx onset
  • Intervention
    • Combination ASA/Plavix x 21 days, then aspirin
  • Comparison
    • Aspirin alone
  • Outcome
    • 90 day subsequent strokes
      • DAPT associated with 3.5% absolute reduction (8.2% vs 11.7%), NNT 29
    • No difference in bleeding events
  • Comment
    • Main criticism: Chinese patients have a larger proportion of undertreated modifiable stroke risk factors i.e. DM and HTN and greater burden of large vessel cerebrovascular disease. Also Chinese population might have polymorphisms in genes regulating Plavix metabolism.
    • How to apply to US population?
• POINT
  • Population
    • 4881 US patients within 12 hours of a minor strokes or TIA
  • Intervention
    • 90 days DAPT and then aspirin
  • Comparison
    • Aspirin monotherapy
  • Outcome
    • Ischemic stroke: Absolute risk reduction of 1.5% in the DAPT group
    • Bleeding: Absolute risk increase of 0.5%, NNH 200
  • Comment
    • Generalizable to US population
    • 90 day DAPT vs 21 in CHANCE!
    • Ongoing THALES trial looking at 30-day, but aspirin/ticagrelor vs aspirin

Statins

• SPARCL
  • Population
    • 4731 patients with prior stroke or TIA
  • Intervention
    • High intensity statin (atorvastatin 80mg daily)
  • Comparison
    • Placebo
  • Outcome
    • Fatal/non-fatal stroke occurrence at 5 years
    • HI Statin group reduced composite primary outcome of fatal or non-fatal stroke at 5 years
    • Overall a 2.2% absolute risk reduction, NNT to prevent one stroke at 5 years is 45.
  • Comment
    • Industry funded
    • Later analyses revealed associated with HI Statin with hemorrhagic stroke
    • Excluded: Non-ambulatory, AF, cardiac emboli, SAH, high LDL > 160 in some centers

Antidepressants?

• FLAME (Lancet 2011): Does early administration of fluoxetine in addition to standard therapy improve recovery after an ischemic CVA?
  • Population
    • 113 patients after acute stroke, randomized to early fluoxetine or placebo
  • Intervention
    • Addition of fluoxetine to post stroke secondary prevention 5-10 days after event
  • Comparison
    • Placebo
  • Outcome
    • 90 day FMMS Scores (measurement of motor recovery)
      • Intervention group has better outcome vs the control group on the FMMS (P = 0.003)
  • Comment
    • Small sample size
    • Short follow up
• FOCUS (Lancet 2018)
  • Population
    • 3127 patients after acute stroke (2-15 days after), mostly ischemic stroke.
  • Intervention
    • Fluoxetine in addition to standard therapy
  • Comparison
    • Placebo
  • Outcome
    • Modified Rankin Scale Scores (mRS) at 6 months
    • No difference between the 2 groups
    • Fluoxetine group has lower rate of depression than placebo (13% vs 17%) but higher rates of bone fractures (2.9% vs 1.5%)
  • Comment
    • Better designed and powered, no benefit in terms of stroke recovery but associated with inc harm.
    • AFFINITY Trial in Australia ongoing, also investigating the use of early SSRI in post-stroke care.