1 / 17

Intravenous tPA in Acute Ischemic Stroke: Evidence and Outcomes

This study reviews the effectiveness of intravenous tPA within 3 hours of stroke onset in reducing disability. Meta-analysis of trials showed a significant decrease in dependency post-treatment.

rusk
Download Presentation

Intravenous tPA in Acute Ischemic Stroke: Evidence and Outcomes

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Evidence in the ED Byron Drumheller, MD Penn Emergency Medicine

  2. Research Question Does intravenous tPA (Alteplase) when given only within 3 hours of the onset of symptoms for acute ischemic stroke according to current inclusion/exclusion criteria result in a greater percentage of patients with none or minimal disability as defined by a modified Rankin Scale 0-1 at 90 days?

  3. Wardlaw et al. Thrombolysis for acute ischaemic stroke (Review). Cochrane Database of Systematic Reviews 2009, Issue 4.

  4. Methods • Systematic Review and Meta-Analysis • Searched MEDLINE, EMBASE, etc and contacted investigators for randomized controlled trials of thrombolysis vs. placebo in acute ischemic stroke • Combined data in intention-to-treat fashion • Multiple outcomes - death, death or dependency, symptomatic intracranial hemorrhage • Calculated odds ratios for thrombolysis vs. placebo

  5. Results • Identified 26 trials of any thrombolytic agent compared with placebo • Outcome: Death or dependency at end of follow up • Modified Rankin Scale of 3-6 • Available from 21 trials • “Thrombolytic therapy, mostly administered up to 6 hours after ischemic stroke, significantly reduced the proportion of patients who were dead or dependent (modified Rankin 3 to 6) at three to six months after stroke (odds ratio (OR) 0.81, 95% confidence interval (CI) 0.73 to 0.90).”

  6. Results • Individual trial details • 4 intra-arterial, 22 intravenous • 4 streptokinase, 11 recombinant tPA, 6 urokinase, 3 desmoteplase • Dose of rtPA • 0.9 mg/kg – 6 • 1.1 mg/kg – 1 • 0.7 or 0.9 mg/kg – 1 • 0.85 mg/kg - 1 • 0.6 mg/kg - 1

  7. Results • Individual trial details • Time to onset • <3 hrs - 2 • <4 hrs - 1 • 3-4.5 hrs - 1 • <6 hrs - 13 • 3-6 hrs - 1 • 3-9 hrs – 3

  8. Results • Individual trial details • Stroke type • All – 7 • Cortical/Lacunar – 2 • ICA/MCA/VBA by angio – 6 • Thrombotic not embolic – 3

  9. Research Question Does intravenous tpa (Alteplase) when given only within 3 hours of the onset of symptoms for acute ischemic stroke according to current inclusion/exclusion criteria result in a greater percentage of patients with none or minimal disability as defined by a modified Rankin Scale 0-1 at 90 days? 0 How many studies?

  10. Results • Intravenous alteplase – 11 studies • 0.9 mg/kg rtPA (0.1 mg/kg bolus, infusion) – 6 studies • Enrolled ANY patients within 3 hours – 3 • All patients within 3 hours – NINDS • Any patients within 3 hours – ATLANTIS, ECASS II

  11. Results • Current inclusion/exclusion criteria • NINDS • Did not exclude patients with >1/3 cerebral hemisphere hypodensity on initial CT • Did not technically excluded patients with brain tumor/AVM, recent neurosurgery, active bleeding • Included patients with mild symptoms NIHSS < 4 • ECASS II • Excluded age>80, coma, hct<25 • Different cutoff for minor stroke, recent seizure or TBI • Did not exclude non-compressible arterial puncture

  12. Results • Inclusion/exclusion criteria • ATLANTIS • Excluded age>80, coma, septic embolus, pericarditis, hct <25 • Different time cutoffs for recent stroke, trauma, biopsy, GI/GU bleeding • Did not exclude >1/3 cerebral hemisphere hypodensity

  13. Research Question • To make any evidence-based conclusion from current data, one must make concessions 1. Include only studies using intravenous recombinant tPA at 0.9 mg/kg with 0.1 mg/kg bolus and 0.8 mg/kg infusion 2. Include data from any patients treated within 3 hours of symptom onset 3. Allow for “minor” differences in inclusion/exclusion criteria

  14. Intravenous tPA only • Is there a difference between agents/doses? • Wardlaw et al. Cochrane Database of Systemic Reviews 2013. - 20 randomized/quasi trials • rtPA 0.9 mg/kg vs. other agents – 2 trials • Haley et al. Stroke 2010 - tPA v TNK (3 doses) • Parsons et al. NEJM 2012 - tPA v TNK (2 doses) • rtPA 0.9 mg/kg v. other dose – 0 trials • 5 trials of rtPA at some dose v other dose

  15. Inclusion/Exclusion • IST-3. Lancet 2012 • 3035 patients treated with rtPA within 6 hours • Used “uncertainty principle” in which patients with “clear indication” for IV tPA were excluded • 53% > 80 years ago, BP up to 220/130

  16. My Meta-Analysis

  17. HUPism While there is no current data that exactly answers the question, the available data specifically addressing whether IV tPA given only within 3 hours of the onset of symptoms for acute ischemic stroke according to current inclusion/exclusion criteria suggests that a greater percentage of patients treated with tPA will achieve no or minimal disability as defined by a modified Rankin Scale 0-1 at 90 days

More Related