Thrombolytics for acute ischemic stroke

Background

see list of all thrombolytic trials in CVA for more details

NINDS Trial (treated within 3hrs)

Benefits:

• 12% absolute risk reduction benefit (NNT = 8-9) at 3 months
• Lower percentage of patients who left hospital severely disabled
• Comparable 3-month mortality rate (even with increased rate of ICH)

Risks:

• 1% increase in mortality
• 5% increase in nonfatal intracranial hemorrhage

ECASS Trial (treated within 4.5hrs)

• Confirmed NINDS findings even when therapeutic window extended to 4.5hr
• As a result AHA/ASA now recommends tPA for patients presenting up to 4.5hr after symptom onset

Studies Required

• Physical exam: NIH Stroke Scale
• Head CT
• CBC (hemoglobin, plt)
• PT/PTT/INR
  • Only need to wait for result if suspicion of abnormal value, patient has received heparin or warfarin, or use of anticoagulants is unknown
• Glucose
• ECG
• Urine pregnancy (pregnancy is relative contraindication)

tPA <3hr

Inclusion Criteria

• Diagnosis of ischemic stroke causing measurable neuro deficit
• Clear onset (last witnessed well) <3hr (see below for extension to <4.5hr)
• Age >18yr

Exclusion Criteria

• Historical
  • Stroke or head trauma in previous 3 months
  • Any history of intracranial hemorrhage
  • Major surgery in the previous 14 days
  • GI or urinary tract bleeding in previous 21 days
  • Myocardial infarction in previous 3 months
  • Arterial puncture at noncompressible site in previous 7 days
• Clinical
  • Spontaneously clearing stroke symptoms
  • Only minor and isolated neurologic signs
  • Seizure at stroke onset
• Persistent SBP >185 or DBP >110 despite treatment
• Use of direct thrombin inhibitors (e.g. dabigatran, argatroban) or direct factor Xa inhibitors (e.g. rivaroxaban, apixaban) with elevated aPTT, INR, or factor Xa assay
• Active bleeding or acute trauma (fracture) on exam
• Labs
  • Platelets <100K
  • Serum glucose <50, >400
  • INR >1.7 or PT >15 sec if on warfarin
  • Elevated PTT if on heparin
• Head CT
  • Evidence of hemorrhage
  • Evidence of multilobar infarction with hypodensity involving >33% of cerebral hemisphere
  • Intracranial neoplasm, AVM, or aneurysm
• Use of dabigatran within 48hrs is relative contraindication

Relative Exclusion Criteria

• Minor or rapidly improving stroke symptoms
• Pregnancy
• Seizure at onset with postictal residual neuro impairments

tPA between 3-4.5hrs

Inclusion Criteria

• Same as for <3hr

Exclusion Criteria

• All of the above plus:
  • Age >80yr
  • Combination of both previous stroke and DM
  • NIHSS score >25
  • Oral anticoagulant use regardless of INR

Administration

Alteplase

• NOTE - in stroke, do not give aspirin until 24 hours after giving tPA, as ASA with tPA does not improve outcomes and increases bleed risk
• Do not give acutely heparin (or any anticoagulation) if giving tPA

Dosing:

• 0.9mg/kg IV (max 90mg total)
  • 10% of dose is administered as bolus; rest is given over 60min
• Neuro check Q15min x 2hr
• No anticoagulation/antiplatelets x 24hr
• Blood pressure (keep SBP <180, DBP <105)

If SBP is >180-230 or DBP is >120:

• Nicardipine 5 mg/hr by slow infusion (50 mL/hr) initially; may be increased by 2.5 mg/hr every 15 minutes; not to exceed 15 mg/hr OR
• Labetalol 10mg IV over 1–2 min; repeat dose q10–20min up to 300mg max OR
• Labetalol 10mg IV followed by infusion at 2–8 mg/min

If BP not controlled by above measures:

• Nitroprusside 0.5–10mcg/kg/min
• Continuous arterial monitoring advised
• Use with caution in patients with hepatic or renal insufficiency

tPA Complications

• Post-tPA Hemorrhage
• Angioedema

See Also

• CVA (Main)
• Post-tPA Hemorrhage in CVA
• NIH Stroke Scale
• List of studies: Thrombolytics in CVA
• Thrombolytics

References

• Hacke W, Kaste M, Bluhmi E, et al: Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med 359(13): 1317, 2008
• ACEP/AAN Guidelines
• AHA/ASA Guidelines