• Three Clinical Trials of Endovascular Therapy for Ischemic Stroke

    • Aug 01, 2013
    • Alexander A. Khalessi, MD

    Editor’s note: The CNS, AANS, SVIN, SNIS & ASNR-endorsed joint response to these 3 clinical trials is available at Neurosurgery®.

    IMS III was a randomized controlled clinical trial involving 656 iv-tPA eligible participants with presenting NIH Stroke Scales greater than 8. Comparison of iv-tPA versus iv-tPA plus mechanical thrombectomy (IAT) cohorts demonstrated no significant difference in three-month functional outcome (mRS 0-2: 38.7% versus 40.8%), mortality (19.1% versus 21.6%), or symptomatic intracranial hemorrhage (6.2% versus 5.9%). However, IMS III yielded important insights into systems of care and the criticality of confirmed large vessel occlusion. Subset analysis showed that patients with large vessel occlusion confirmed by pre-procedural CTA (47% of total study population) had statistically improved Rankin outcomes at 3 months; CTA patients also received IA intervention 20 minutes faster. Limitations of the study include long accrual time, median delays of 80 minutes from iv-tPA to endovascular intervention in the IAT arm, and next-generation thrombectomy devices such as Solitaire FR (Covidien) were used in only four patients.

    SYNTHESIS was a multi-center Italian trial that randomized 362 patients presenting with acute ischemic stroke symptoms to iv-tPA within 4.5 hours (ECASS III standard) versus endovascular therapy (IAT) within 6 hours. Critically, the authors provided no technical data of endovascular revascularization success, and only 56/181 IAT patients received mechanical thrombectomy. The remaining IAT patients received no treatment (16 patients) or IA-tPA with wire manipulation (109 patients). Heterogeneity in the IAT arm was compounded by the absence of pre-procedural imaging to confirm a large-vessel occlusion or a minimum NIHSS for study inclusion. Therefore, the SYNTHESIS study is very different from current North American endovascular practice, and failed to demonstrate benefit for IAT. Despite these limitations of technique variations and IAT temporal disadvantage, SYNTHESIS demonstrated no IAT safety concerns.

    MR RESCUE enrolled 118 patients presenting within 8 hours with a confirmed anterior circulation stroke. The trial employed MR perfusion-diffusion mismatch to assess possible mechanical revascularization benefit in the setting of a favorable MRI-based penumbral profile. Though endovascular therapy failed to demonstrate a statistical benefit in the penumbral and non-penumbral groups by the 3-month mRS primary endpoint, the study was severely limited by the revascularization success rate of first generation thrombectomy devices used. Successful revascularization occurred in 41% of cases and often was a TICI 2a result; this falls short of the modern standard with stentriever and next-generation aspiration technologies. Importantly, patients with adequate reperfusion demonstrated mean improvements in 3-month mRS (3.2 [2.6-3.8] versus 4.1 [3.7-4.5], P=0.04) and median absolute infarct growth (9.0 versus 72.5 mL, P<0.001). Thus, improvement in revascularization rates with newer devices may demonstrate benefit for using penumbral imaging with IAT that is not observed in MR RESCUE.

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