Acute stroke: doubt cast on benefit of prethrombectomy IV alteplase

  • Yang P & al.
  • N Engl J Med
  • 6 May 2020

  • curated by Susan London
  • Clinical Essentials
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Takeaway

  • Patients with large-vessel occlusion acute ischemic stroke had a noninferior neurologic outcome when they underwent endovascular thrombectomy directly, without receiving intravenous (IV) alteplase first.

Why this matters

  • Alteplase is costly and carries bleeding risk.
  • Editorial points to a "generous" margin for noninferiority, says the confidence intervals did not exclude a benefit of ~20% with combination therapy, and urges continued adherence to current guidelines recommending prethrombectomy alteplase in all eligible patients.

Key results

  • Vs thrombectomy preceded by IV alteplase, thrombectomy alone yielded noninferior distribution of modified Rankin scale scores at 90 days:
    • Median score (interquartile range) of 3 (2-5) for each;
    • Adjusted common OR, 1.07 (95% CI, 0.81-1.40); and
    • P=.04 for noninferiority.
  • However, thrombectomy alone netted lower rates of:
    • Successful reperfusion before thrombectomy (2.4% vs 7.0%) and
    • Successful reperfusion overall (79.4% vs 84.5%).
  • Groups were similar on 90-day mortality (17.7% vs 18.8%; P=.71), other serious adverse events (e.g., intracranial hemorrhage, infarction in new territory).

Study design

  • Multicenter noninferiority randomized controlled trial among 656 patients in China with acute ischemic stroke from large-vessel occlusion in anterior circulation (DIRECT-MT trial).
  • Randomization: endovascular thrombectomy with vs without preprocedural IV alteplase (0.9 mg/kg; ≤4.5 hours after symptom onset).
  • Main outcome: distribution of modified Rankin scale scores (noninferiority: lower boundary of 95% CI of adjusted common OR ≥0.8).
  • Funding: Chinese government; Wu Jieping Medical Foundation.

Limitations

  • Protocols followed 2015 guidelines.
  • Larger noninferiority margin, smaller sample.
  • Region-specific triage system, consent process.