Response to Letter Regarding Article, "Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous Thrombolysis".

Response to Letter Regarding Article, “Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous Thrombolysis” We would like to thank Kamtchum-Tatuene et al for commenting on our recently published meta-analysis evaluating the potential interaction of pretreatment with intravenous thrombolysis (IVT) on the association of endovascular reperfusion therapies (ET) with functional outcome in patients with emergent largevessel occlusion (ELVO). We conducted this study after reading another meta-analysis on the topic supporting that only in the subgroup of patients pretreated with IVT, ET was associated with a higher likelihood of functional independence compared with standard therapy. This finding drew our attention, as no such interaction was detected in the individual randomized controlled clinical trials including patients with and without IVT pretreatment. Even though our systematic review and meta-analysis provide additional evidence that ET is effective for patients with acute ischemic stroke (AIS) with anterior circulation ELVO independent of IVT pretreatment, we disagree with the notion that at present ET can be considered as an independent and initial treatment option for all patients with AIS. Current American Heart Association/American Stroke Association guidelines advocate that patients with AIS are eligible for ET with stent retrievers only if they have received previous treatment with IVT within the therapeutic window of 4.5 hours (class I, level of evidence A). They also report that ET may be offered to patients with ELVO and contraindication to IVT with a weak strength of recommendation (class IIa, level of evidence C). Therefore, the answer to the question of whether the initial treatment with IVT is still worthwhile for eligible patients with AIS remains positive, even for those with ELVO that could be readily offered ET. From practical standpoint and to answer the question of younger colleagues mentioned in the letter, the decision to give IVT can be made expeditiously (Helsinki model) and should be made at the time of noncontrast computed tomography (CT) that precedes CT angiography. If one waits for imaging to show ELVO, it may create an illusion that it is faster to take patient straight to the endovascular suite than to deliver tissue-type plasminogen activator to bedside. In fact, stroke teams after having performed quick neurological examination on the way to CT, should be able to mix tissue-type plasminogen activator in CT immediately after its completion, start IVT in parallel with arming contrast injector, and complete CT angiography and then take the eligible patient to ET. Our findings have also been confirmed by a recent individual patient data meta-analysis from 5 randomized controlled clinical trials with stent retrievers that was conducted by the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration. This study also highlights that there is no interaction of pretreatment with IVT on the efficacy of ET (compared with standard therapy) in terms of improving functional outcome. Consequently, there is no reason to withhold ET from ELVO patients with contraindications to IVT within the therapeutic window of 4.5 hours or to ELVO patients within the time interval of 4.5 to 6 hours from stroke onset (outside the therapeutic of IVT, but within the time window of ET). Pending further randomized controlled clinical trials data, ET should be offered to all patients with ELVO independent of pretreatment with systemic thrombolysis, whereas IVT should never be delayed in favor of imaging ELVO and should be administered swiftly to all patients with AIS eligible for tissue-type plasminogen activator without delaying access to ET. This will take truly a team effort to jointly deliver evidencebased practices of vascular neurology and neurointervention.