Outcomes of Mechanical Thrombectomy in the Early (<6-hour) and Extended (≥6-hour) Time Window Based Solely on Noncontrast CT and CT Angiography: A Propensity Score–Matched Cohort Study

DISCUSSION

This retrospective cohort provides additional evidence from a real-world setting that clinical evaluation and noncontrast CT-ASPECTS in the extended time window are sufficient to achieve favorable outcome rates. Safety end points for symptomatic intracranial hemorrhage and death at 90 days were similar for both time windows. Likewise, successful revascularization was achieved in >90% regardless of the time windows. A favorable functional outcome was more frequently achieved in the early time window. This observation remained evident even after matching CT-ASPECTS variables, reflecting the predominant role of time in revascularization. However, still, 1 of 3 patients in the extended time window achieved a favorable functional outcome. These observations align with Santos et al,¹³ who also analyzed a cohort selected solely by noncontrast CT and CTA. They compared 186 patients from the 0- to 6-hour window with 63 patients in the time window beyond 6 hours. While applying strict inclusion criteria (NIHSS > 11, CT-ASPECTS > 6, and premorbid mRS < 2 for the extended time window), the authors observed a favorable functional outcome in 57% and 65.1% in the 0- to 6-hour and beyond the 6-hour time windows, respectively. Mortality and symptomatic intracranial hemorrhage rates were equal across time windows.¹³

Advanced imaging such as CT perfusion or diffusion-weighted MR imaging allows the preselection of those patients with small cores with a higher likelihood of a beneficial outcome from mechanical thrombectomy. This effect becomes particularly apparent in the extended time window. Patients beyond 6 hours of symptom onset have comparatively small cores, but without intervention, they are not likely to withstand hypoperfusion resulting in cerebral infarction and neurologic decline. Albers¹⁴ appropriately illustrated the role of timing and imaging on patient selection together with inherent absolute treatment effects when discussing the late window paradox. Albers postulated that patients who withstand the first 6 hours without significant infarctions (core volumes) have likely a favorable status due to good collateral supply. On the other hand, patients with poor collaterals are very likely to have significant infarctions even in the early time window. Early deteriorators are patients who do not benefit from mechanical thrombectomy despite timely treatment. Patients with poor collateral status and early infarctions are very unlikely to be candidates for mechanical thrombectomy in the extended time window. In contrast, patient selection in the early time window is likely to be more liberal. Therefore, patients selected in the extended time window have an a priori more favorable basis, translating into a relatively benign functional outcome of this particular subgroup.¹⁴

CT perfusion imaging performed within 6 hours of symptom onset may overestimate the infarct core.¹⁵ Thus, CT perfusion imaging in the early time window requires careful interpretation. For the extended time window, to date, only DEFUSE-3 and DAWN provide class I recommendations. In both trials, patients underwent advanced imaging to screen for core infarct volumes, and patient selection was based on predefined cutoffs.^8,9 Despite the awareness of stroke care inequities between urban and rural areas,¹⁶ the current literature lacks a discussion on strategies for patients eligible for mechanical thrombectomy requiring long-distance transfers. During the study period, February 2016 to August 2020, two hundred thirty-seven/417 (56.8%) mechanical thrombectomies were performed in transferred patients. Among the early time window, transferred patients constituted 52.0% of all cases, whereas transferred patients even constituted 63.9% of all cases among the extended time window. In our health care system, transfer times regularly exceed 1 hour due to the long distance despite an internal flight air ambulance system. To date, it is unknown whether transferred patients should undergo repeat imaging to update CT-ASPECTS and rule out hemorrhage or even undergo advanced imaging to estimate the infarct core and guide patient selection.

Furthermore, only a subset of affiliated rural hospitals are certified primary stroke centers capable of providing timely advanced imaging. Contrasting the ideal stroke care system incorporating timely transportation and timely availability of advanced imaging with a stroke care system, in large part, also covering rural areas highlights 2 aspects that require reiterated adjudication by stroke quality frameworks. First, suspending advanced imaging should guide patient selection in both the early and extended time windows. Second, delaying mechanical thrombectomy by repeat imaging unless there is severe neurologic decline may result in fatality due to herniation or hemorrhage.

Recently, Nogueira et al¹⁰ found CT perfusion–based patient selection not superior to standardized noncontrast CT and CTA in terms of functional-outcome prediction. These observations, together with real-world data such as presented in the current study, challenge the demand for advanced imaging to guide patient selection and justify patient selection based purely on favorable CT-ASPECTS, even in the extended time window. The selection of patients with favorable CT-ASPECTS is shown in Fig 2. Notably, the selection of patients with large-vessel occlusion for mechanical thrombectomy using advanced imaging may increase the relative proportion of patients achieving functional independence but might compromise the absolute number of patients potentially benefitting from this treatment by excluding patients who might have benefitted.

Lowering the threshold for performing mechanical thrombectomy has also been debated for patients presenting with poor CT-ASPECTS such as CT-ASPECTS < 6. In this context, older age and large-core infarcts do not uniformly present a contraindication for mechanical thrombectomy. Instead, a subset of patients with large-core infarcts undergoing mechanical thrombectomy still achieve a favorable functional outcome.^{17⇓⇓⇓–21} Whether sparing of either the deep or superficial MCA territories provides a better outcome is still controversial.^22,23 Partial reperfusion of distinct areas such as the motor-eloquent cortical area appears to outweigh the degree of partial reperfusion.²⁴ It remains uncertain whether advanced imaging would identify these patients better or exclude patients who could benefit.

Mechanical thrombectomy beyond the 6-hour time window with patient selection based on advanced imaging appears cost-effective.^25,26 Providing timely interpretation of perfusion-based advanced imaging modalities has been challenging for every stroke center. It has led to the development of outsourced solutions and automated interpretation platforms. However, standardized cloud-based services to assess core and penumbra on CT or MR perfusion are associated with a substantial financial burden. This study shows that selection of patients with large-vessel occlusion strokes for thrombectomy with favorable CT-ASPECTS even in the extended time window is feasible, without using advanced imaging modalities.

In summary, absolute treatment effects become lower with less stringent preselection criteria. However, withholding mechanical thrombectomy due to lack of advanced imaging does not appear justifiable for those patients with favorable CT-ASPECTS irrespective of the time window. Additional investigation is required to determine the value of advanced imaging in patients in extended time windows and those with large-core infarcts on presentation.