EBQ:Studies List of Thrombolytics for Acute Stroke

MAST-Italy (n = 622) [1]

  • Time to treatment: < 6 hours
  • Results: Increased early death (OR 2.7), Slight decrease 6 m disability (OR 0.5)
  • Overall: No benefit

ECASS (n = 620) [2]

  • Time to treatment: < 6 hours, Notable inclusion: Moderate - severe hemispheric stroke
  • Results: No difference in disability or death
  • Overall: No benefit

NINDS-1 (n = 291) [3]

  • Time to treatment: < 3 hours
  • Results: No difference NIHSS improvement by 4 pts or resolution of deficits at 24 hours
  • Overall: No benefit

NINDS-2 (n = 333) [4]

  • Time to treatment: < 3 hours
  • Results: Initial primary outcome was to be improvement in functional and stroke scores (of 20%). This was changed, post-hoc, to dichotomous favorable vs. unfavorable outcome. Original primary outcome result not reported.
  • Overall: Benefit = NNT of 8 for 'favorable’ outcome measure

MAST-Europe (n = 310) [5]

  • Time to treatment: < 6 hours
  • Notable Inclusion: Mod-severe stroke, MCA territory only
  • Outcome: No difference combined disability/death at 6 months; increased ICH (21% vs. 3%) and statistically nonsignificant increased mortality (47% vs. 38%)
  • Overall: Harmful (STOPPED EARLY DUE TO ICH AND MORTALITY)

ASK (n = 340) [6]

  • Time to treatment: <4h (small % 4-5h)
  • Outcome: No difference combined disability/death at 3 months; slightly decreased disability and increased mortality at 3 months, OR 1.83 (1.14-2.93)
  • Overall: Harmful (STOPPED EARLY DUE TO MORTALITY)

ECASS-II with tPA (n = 800) [7]

  • Time to treatment: <6h (20% < 3 hours)
  • Outcome: No difference in favorable outcomes (modified Rankin Scale) at 3 months
  • Overall: No benefit

ATLANTIS-B with tPA (n = 613) [8]

  • Time to treatment: 20% 3-4 h, 70% 4-5
  • Outcome: No difference, favorable outcome at 3 months; increased ICH (7% vs. 1%) and nonsignificant increase in mortality (11% vs. 7%)
  • Overall: Harmful (STOPPED EARLY BECAUSE “unlikely to prove beneficial)

ATLANTIS-A with tPA (n = 142) [9] [10]

  • Time to treatment: Initially 0-6 hours, stopped enrolling 0-3hrs and only enrolled 0-5hrs based on NINDS result
  • Outcome: Improvement in NIHSS score (4 pts) at 24h favored lytics (40% vs. 21%, p=0.02) but at 1 month favored placebo (75% vs. 60%, p=0.05). Increased ICH with tPA (11% vs. 0%) and increased mortality at 3 months (23% vs. 7%)
  • Overall: Harmful (STOPPED EARLY DUE TO HARM)

DIAS-2 with desmoteplase (n = 193) [11]

  • Time to treatment: 3-9 hours Notable inclusion: reversible ischemic penumbra on MR or CT
  • Outcome: No difference in favorable outcomes; Nonsignificant increase in mortality for high dose desmoteplase group (stopped early for harm then restarted)
  • Overall: No benefit

ECASS III with tPA (n = 821) [12]

  • Time to treatment: 3-4.5 h
  • Outcome: More favorable outcomes with tPA (OR 1.34, 1.02-1.76), mortality no difference
  • Overall: Benefit = NNT of 15 for ‘favorable’ outcomes

IST-3 with tPA (n = 3035)[13]

  • Time to treatment: 0-6 h
  • Outcome: Short term mortality increase of 4% (1st week); no difference found in primary outcome (% alive and independent at 6 months); authors report a secondary analysis favoring thrombolytics
  • Overall: No benefit

See Also

External Links

References

  1. ↑ Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial--Italy (MAST-I) Group. 1995;346(8989):1509–1514
  2. ↑ Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). 1995;274(13):1017–1025
  3. ↑ Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581–1587. doi:10.1056/NEJM199512143332401.
  4. ↑ Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581–1587. doi:10.1056/NEJM199512143332401
  5. ↑ Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke T Trial--Italy (MAST-I) Group. The Lancet. 1995;346(8989):1509–1514.
  6. ↑ Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. 1996;276(12):961–966.
  7. ↑ Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. 1998;352(9136):1245–1251
  8. ↑ Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. 1999;282(21):2019–2026
  9. ↑ ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. 2002;33(2):493–495
  10. ↑ Clark WM, Albers GW, Madden KP, Hamilton S. The rtPA (Alteplase) 0- to 6-Hour Acute Stroke Trial, Part A (A0276g) : Results of a Double-Blind, Placebo-Controlled, Multicenter Study. Stroke. 2000;31(4):811–816. doi:10.1161/01.STR.31.4.811
  11. ↑ Hacke W, Furlan AJ, Al-Rawi Y, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion–diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009;8(2):141–150. doi:10.1016/S1474-4422(08)70267-9
  12. ↑ Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke. The New England Journal of Medicine. 2008;359(13):1317–1329. doi:10.1056/NEJMoa0804656.
  13. ↑ Sandercock PP, Wardlaw JMJ, Lindley RIR, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. The Lancet. 2012;379(9834):2352–2363. doi:10.1016/S0140-6736(12)60768-5.
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