What are the implications of the TICH-2 (Tranexamic Acid for Intracerebral Hemorrhage 2) trial on the use of Tranexamic Acid (TXA) in patients with spontaneous intracerebral hemorrhage?

Implications of the TICH-2 Trial on Tranexamic Acid Use in Spontaneous Intracerebral Hemorrhage

The TICH-2 trial demonstrated that tranexamic acid (TXA) does not improve functional outcomes at 90 days in patients with spontaneous intracerebral hemorrhage (ICH), despite modestly reducing hematoma expansion. Based on this evidence, TXA is not recommended for routine use in spontaneous ICH management.

Key Findings from TICH-2

• Primary Outcome: No significant difference in functional status (modified Rankin Scale) at 90 days between TXA and placebo groups (adjusted odds ratio 0.88,95% CI 0.76-1.03) 1

• Secondary Outcomes:

  • Modest reduction in hematoma expansion with TXA
  • Fewer early deaths (by day 7) in the TXA group (aOR 0.73,95% CI 0.53-0.99)
  • No difference in 90-day mortality
  • Fewer serious adverse events with TXA
  • No increase in thromboembolic events or seizures 1

Current Guideline Recommendations

The European Society of Intensive Care Medicine (2021) makes no recommendation regarding TXA use in non-traumatic ICH, noting "moderate evidence of no effect" 2. They state:

• TXA shows no change in mortality (RR 1.02,95% CI 0.88-1.19)
• No improvement in poor functional outcome (RR 0.98,95% CI 0.93-1.04)
• Other outcomes including stroke, MI, VTE, seizures, and length of stay were similar 2

Similarly, the 2022 AHA/ASA guidelines state that "the effectiveness of TXA to improve functional outcome is not well established" in patients with spontaneous ICH 2.

Subgroup Analysis and Special Populations

Antiplatelet-Associated ICH

In patients with pre-ICH antiplatelet therapy (26.3% of TICH-2 participants):

• TXA reduced hematoma expansion (adjusted OR 0.61,95% CI 0.41-0.91)
• No significant interaction between pre-ICH antiplatelet therapy and TXA effect (P interaction=0.248) 3
• Despite this reduction in hematoma expansion, no improvement in functional outcomes was observed

Surgical Intervention

For ICH patients requiring neurosurgical intervention:

• TXA did not reduce the frequency of neurosurgical intervention (4.9% TXA vs 5.5% placebo)
• No improvement in outcomes in surgically treated patients (OR 0.79,95% CI 0.30-2.09)
• No reduction in postoperative hematoma volume with TXA 4

Limitations of TICH-2

Several factors may have limited the potential efficacy of TXA in TICH-2:

1. Timing: Most participants were enrolled >4.5 hours after symptom onset, potentially beyond the therapeutic window 1

2. Heterogeneous population: Included patients with very large strokes who may have had poor prognosis regardless of intervention 1

3. Modest effect on hematoma expansion: While statistically significant, the reduction in expansion may have been too small to translate to clinical benefit 5

Clinical Implications and Future Directions

Despite TXA's favorable safety profile with no increase in thromboembolic complications, current evidence does not support its routine use in spontaneous ICH. Future research should focus on:

• Earlier treatment (within 1-2 hours of symptom onset)
• Identifying specific subpopulations most likely to benefit
• Combining TXA with other interventions to maximize benefit

The Hemorrhagic Stroke Academia Industry Roundtable recommends that future trials of hemostatic agents like TXA should prioritize patient-centered clinical outcomes rather than solely focusing on radiographic measures of hematoma expansion 2.

In conclusion, while TXA appears safe in ICH patients, the TICH-2 trial and subsequent analyses do not support its routine use for improving functional outcomes in spontaneous ICH.