QUESTION 1: Do the benefits of TPA outweigh the risks of symptomatic ICH (sICH)?

Big picture:

NNT for TPA <3hrs is 1:3 for a benefit (MRS improved 1 pt)

  • Critics dismiss 1-point move as sig outcome, but it is a large QOL change.

NNT for TPA within 4.5 hrs is 1:6

Best outcomes are within 90min. Mortality increases after 4.5 hours.

NINDS-1 (1995)

  • Significant benefit (i.e. MRS 0/1 from 26 -36 %, OR 1.7) but hemorrhage rate 0.6 vs 6.4% in TPA group

Data re-analysis – 2004

  • Still found data for benefit

Clarified RF for bleeding risk (0 RF risk 1.8%, 1 RF is 4.9%, >1 RF risk is 21%)

  • sICH RF: NIHSS >20, Age >70, Ischemic changes on CT, Glucose >300
  • Can/should use THRIVE score to estimate bleeding risk (on MDcalc)

SITS-MOST Study: Validated practical application of rt-TPA in community setting with improved outcomes. 4.6% sICH.

ECASS-3 expanded TPA window to 4.5 hours w/ a dichotomous variable of MRS 0/1 or 2+. Increased ICH risk, but benefit is preserved.

  • 52% vs 45% w/ MRS 0/1 (CI low end is 1.02 for OR)
  • sICH 2.4% vs 0.2. No mortality difference. All ICH was 27% vs 17%.

GWTG Stroke program analysis

  • Validated 90 minute cut-off associated w/ decrease mortality vs 90-180
  • sICH 4-5%

Sinai sICH rate around 4% overall, but we need to be giving patients more individualized sICH risks than 6.8% for everyone.

Updated exclusion criteria includes more folks (see last two pages for summary).

  • Example: Glucose >400 removed, glucose <50 not contra if sx persist post correction

QUESTION 2: Does neurothrombectomy offer benefit? Yes

Initial studies with Mercy device did not demonstrate benefit

Newer devices (Solitaire, Stentreiver) with much better outcomes: NNT 2.6

AHA revised their endovascular treatment guidelines in 2015

DAWN Trial just published in NEJM, Nogueira et al

  • Thrombectomy 6-24hrs (ie out of TPA window) for occlusion of ICA or MCA
  • Functional indep 49% vs 13% std of care (NNT 2.8 for functional indep)
  • sICH 6% vs 3% w/ no mortality diff

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