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Time Window for Thrombectomy After Stroke Can Be Extended for Some Patients

Key findings

  • Patients with large vessel stroke who have a region of brain tissue that is ischemic but not yet infarcted may respond well to endovascular thrombectomy performed 6-16 hours after stroke onset
  • Compared with standard medical therapy alone, ET plus standard medical therapy resulted in less disability and a higher rate of functional independence at three months
  • The 90-day mortality rate was lower with ET plus medical therapy than with medical therapy alone

The DAWN trial recently showed that the time window for endovascular thrombectomy (ET) can be extended to 24 hours after stroke onset. In that trial, perfusion imaging was used to select patients who had a disproportionately severe clinical deficit compared with the size of the infarct.

In a separate trial with a broader population named the DEFUSE 3 trial, Thabele M. Leslie-Mazwi, MD, a specialist in neurovascular and neuroendovascular care at Mass General, and colleagues have confirmed and extended those findings. Their report is published in The New England Journal of Medicine.

The researchers conducted a randomized, open-label trial funded by the NIH at 38 U.S. medical centers. Beginning in May 2016, the researchers assigned 182 stroke patients to ET plus standard medical therapy or standard medical therapy alone. ET was performed six to 16 hours after the patient was last known to be well. Intravenous tissue plasminogen activator was allowed if begun within 4.5 hours after symptom onset.

Patients were eligible if they had occlusion of the cervical or intracranial internal carotid artery or the proximal middle cerebral artery on computed tomography angiography or magnetic resonance angiography. Participants were also required to have a region of tissue that was ischemic but not yet infarcted: initial infarct volume (ischemic core) <70 mL, a ratio of ischemic tissue volume to initial infarct volume ≥1.8, and an absolute volume of potentially reversible ischemia (penumbra) ≥15 mL on CT perfusion or MRI perfusion or diffusion scans.

The volume of the ischemic core and penumbral regions was estimated from the images using the same automated image postprocessing system that was used in the DAWN trial.

In June 2017, when the results of DAWN were announced, the NIH requested an early interim analysis of DEFUSE 3. That analysis showed that the prespecified efficacy boundary had been exceeded, so the trial was ended early.

The primary efficacy outcome in DEFUSE 3 was the ordinal score on the modified Rankin Scale (mRS). The interim analysis showed that ET plus standard medical therapy was three times more likely than standard medical therapy alone to be associated with a favorable mRS score at 90 days (adjusted odds ratio, 3.36; 95% confidence interval (CI), 1.96–5.77; < .001).

The secondary efficacy outcome was functional independence at day 90 (mRS score 0–2). The percentage of participants achieving functional independence was 45% with ET and 17% with medical therapy alone (risk ratio, 2.67; 95% CI, 1.60–4.48; P < .001).

The mortality rate at 90 days was 14% with ET and 26% with medical therapy alone (= .05). The incidence of serious adverse events and the rate of symptomatic intracranial hemorrhage within 36 hours did not differ significantly between the groups.

The authors comment that DEFUSE 3 enrolled patients who had larger core infarctions than those in the DAWN trial and included patients with milder stroke symptoms. Thus, DEFUSE 3 both confirms that the window for ET can be extended and suggests that a broader population is eligible based on perfusion imaging.

45%
Patients who were functionally independent at day 90 after endovascular therapy

14%
90-day mortality rate after ET

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Related topics

Related

The 2018 AHA/ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke (AIS) feature protocols of stroke care, including intravenous and intra-arterial therapies, in pre- and in-hospital settings. Thabele Leslie-Mazwi, MD, specialist in Neuroendovascular and Neurocritical care at Mass General, was one of the authors of the new guidelines, last updated in 2013, which notably expand the window on when thrombectomies can be performed.

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Patients with large vessel stroke may be eligible for endovascular thrombectomy, but transfer to a comprehensive stroke center is often delayed. Mass General physicians have shared the algorithm they use for induced hypertension, a strategy to save viable brain tissue until reperfusion can occur.