ATTEST-2 Trial: Tenecteplase vs. Alteplase for Stroke

ATTEST-2 Trial — Comparing Tenecteplase and Alteplase for Acute Stroke Management

Introduction

In recent years, the quest for optimal treatments for acute ischemic stroke has intensified, with the goal of improving outcomes and accessibility of care. The ATTEST-2 trial, published in 2024, sought to answer whether tenecteplase is non-inferior or even superior to alteplase when administered within 4.5 hours of stroke onset.

Objective

The primary objective of ATTEST-2 was to determine if tenecteplase (0.25 mg/kg) could match or surpass the effectiveness of alteplase (0.9 mg/kg) for treating acute ischemic stroke. The study included patients aged 18 and above who were eligible for intravenous thrombolysis within the critical 4.5-hour treatment window.

Study Design and Participants

This was a randomized, parallel-group, open-label trial with a substantial sample size of 1,777 patients:

  • Tenecteplase Group: 885 patients received 0.25 mg/kg tenecteplase.
  • Alteplase Group: 892 patients received 0.9 mg/kg alteplase.

The exclusion criteria were strict, ensuring patients with any major medical condition that could impact survival or availability for day-90 follow-up were omitted.

Primary Outcome

The primary outcome focused on the distribution of Modified Rankin Scale (mRS) scores at day 90, measuring levels of disability:

  • The score distribution was 1.07 (90% CI: 0.90 to 1.27).
  • Statistical results indicated P < 0.0001 for non-inferiority and 0.43 for superiority, affirming that tenecteplase was non-inferior to alteplase.

Secondary Outcomes

The trial also examined several secondary outcomes:

  1. Excellent Neurological Recovery (mRS score 0–1 at day 90):
  • Tenecteplase Group: 44%
  • Alteplase Group: 42%
  • Results showed P = 0.0018 for non-inferiority and 0.40 for superiority, with an odds ratio (OR) of 0.66.
  1. Independent Neurological Recovery (mRS score 0–2 at day 90):
  • Tenecteplase Group: 68%
  • Alteplase Group: 65%
  • Results showed P = 0.14 and an OR of 0.23.

Key Findings and Conclusion

The findings reveal that tenecteplase (0.25 mg/kg) is non-inferior to alteplase (0.9 mg/kg) when administered within 4.5 hours of stroke symptom onset. This supports tenecteplase as a preferable choice for thrombolysis in acute ischemic stroke, particularly in cases where quick and convenient administration is critical, such as during interhospital transfers.

The ATTEST-2 trial’s results suggest a promising shift in the stroke management landscape, offering clinicians more flexibility without compromising patient outcomes.

Final Thoughts

For healthcare providers, especially those involved in stroke care, ATTEST-2 highlights the potential of tenecteplase as a viable and effective alternative to alteplase. As more studies further explore tenecteplase’s role, it could become a standard in acute ischemic stroke management, improving care efficiency and accessibility.

References

Muir K. W. et al. Lancet 2024;23(11):1087-1096.

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