Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct

SOURCE: NEW ENGLAND JOURNAL OF MEDICINE

November 11, 2017

BACKGROUND

The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy.

Previous randomized trials that involved patients with acute stroke1-6 showed that endovascular thrombectomy had a clinical benefit when it was performed within 6 hours after the onset of stroke symptoms7 and that the benefit diminished as the interval between the time that the patient was last known to be well and thrombectomy increased.8 For the purposes of determining eligibility for thrombolysis or thrombectomy, the time that the patient was last known to be well has typically been considered to be the time of stroke onset, including among patients who wake up with stroke symptoms or have an uncertain time of stroke onset. There is limited information on the effect of thrombectomy that is performed more than 6 hours after the time that the patient was last known to be well, particularly among patients with ischemic brain tissue that has not yet undergone infarction and may be salvaged with reperfusion. Patients with brain tissue that may be salvaged with reperfusion can be identified by the presence of a clinical deficit that is disproportionately severe relative to the volume of infarcted tissue on imaging studies (see Section S3 in the Supplementary Appendix, available with the full text of this article at NEJM.org).9

Results of previous nonrandomized studies have suggested that patients who have a mismatch between the volume of brain tissue that may be salvaged and the volume of infarcted tissue could benefit from reperfusion of occluded proximal anterior cerebral vessels, even when the reperfusion is performed more than 6 hours after the patient was last known to be well.10,11 In the DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) trial, we compared endovascular thrombectomy plus standard medical care with standard medical care alone for the treatment of patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct.

METHODS

We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days.

RESULTS

A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00).Full Text of Results…

CONCLUSIONS

Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283.)

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