Thrombectomy 6-16 hours after ischemic stroke symptom onset may reduce disability in patients with salvageable brain tissue identified by perfusion imaging

EBM Focus - Volume 13, Issue 6

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Reference: DEFUSE 3 trial (N Engl J Med 2018 Jan 24 early online) (level 2 [mid-level] evidence)

  • Two recent trials show that endovascular thrombectomy > 6 hours after ischemic stroke symptom onset reduces disability in patients with evidence of salvageable brain tissue. We reviewed the DAWN trial in a previous EBM Focus issue.
  • Here, we review the DEFUSE 3 trial, in which 182 patients with evidence of salvageable brain tissue identified by perfusion imaging and who were last known to be well 6-16 hours previously were randomized to thrombectomy plus standard medical therapy vs. standard medical therapy alone.
  • At 90 days, the thrombectomy group had greater rates of functional independence (45% vs. 17%, p < 0.001, NNT 4) and lower mortality (death in 14% vs. 26%, risk ratio 0.55, 95% CI 0.3-1.02).
  • The results of the two trials are incorporated in the 2018 AHA/ASA stroke guidelines, which now include recommendations for thrombectomy 6-24 hours after time since last known well in appropriate patients.

Endovascular thrombectomy after acute ischemic stroke can restore blood flow in hypoperfused tissue that is not yet infarcted and thus reduce disability. Thrombectomy within 6 hours of symptom onset in eligible patients has been recommended for several years, and 2 recent trials have demonstrated that thrombectomy after 6 hours may reduce disability in patients with evidence of salvageable brain tissue. The DAWN trial, reviewed in a recent EBM Focus issue, defined evidence of salvageable brain tissue as disproportionately severe clinical deficits compared to ischemic core volume on imaging. Here, we review the DEFUSE 3 trial, which identified potentially salvageable brain tissue based on perfusion imaging criteria. The 182 included patients had occlusion of the proximal middle cerebral artery or cervical or intracranial internal carotid artery, core volume < 70 mL, and were last known to be well 6-16 hours previously. The patients were randomized to mechanical thrombectomy with any FDA-approved device plus standard medical therapy (SMT) vs. SMT alone and followed for 90 days. Stent retrievers were used in 80% of the patients allocated to thrombectomy. Outcome assessors were blinded to patient allocation, but patients and treating physicians were not.

Reperfusion ≥ 50% on angiography (modified Thrombolysis in Cerebral Infarction grade 2b/3) was achieved in 76% of patients who had thrombectomy. The thrombectomy group had better functional outcomes at 90 days than the SMT group, with functional independence (modified Rankin Scale score 0-2) in 45% vs. 17% (p < 0.001, NNT 4) and death in 14% vs. 26% (risk ratio 0.55, 95% CI 0.3-1.02). Rates of symptomatic intracranial hemorrhage within 36 hours were not significantly different between groups (7% vs. 4%). Consistent results for functional independence at 90 days were observed in post-hoc subgroup analyses of 112 patients who met eligibility criteria for the DAWN trial and 70 patients who did not.

The lack of blinding of patients and treating physicians introduces a possible source of bias. Another concern is how widely applicable these results are, as 107 additional patients were considered but did not meet imaging criteria and perfusion imaging was required to identify potentially salvageable brain tissue. The latter concern will be alleviated as more centers expand imaging capabilities and technology progresses. Finally, both the DEFUSE 3 and DAWN trials were stopped before reaching their planned sample sizes after reaching pre-specified criteria demonstrating efficacy. The early termination in the DEFUSE 3 trial was based on an unplanned interim analysis and this may potentially overestimate the beneficial effect of thrombectomy. Overall, the DEFUSE 3 and DAWN trials provide compelling evidence that thrombectomy > 6 hours after the patient was last known to be well may be beneficial in patients who have evidence of salvageable brain tissue. These results are incorporated in the 2018 AHA/ASA stroke guidelines, which now include recommendations for thrombectomy in the 6-24 hour window in appropriate patients.

For more information, see the topic Endovascular therapy for acute stroke in DynaMed Plus. DynaMed users click here.


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