Occurrence and Predictors of Futile Recanalization following Endovascular Treatment among Patients with Acute Ischemic Stroke: A Multicenter Study

摘要

BACKGROUND AND PURPOSE: Although recanalization is the goal of thrombolysis, it is well recognized that it fails to improve outcome of acute stroke in a subset of patients. Our aim was to assess the rate of and factors associated with "futile recanalization," defined by absence of clinical benefit from recanalization, following endovascular treatment of acute ischemic stroke. MATERIALS AND METHODS: Data from 6 studies of acute ischemic stroke treated with mechanical and/or pharmacologic endovascular treatment were analyzed. "Futile recanalization" was defined by the occurrence of unfavorable outcome (mRS score of 3 at 1–3 months) despite complete angiographic recanalization (Qureshi grade 0 or TIMI grade 3). RESULTS: Complete recanalization was observed in 96 of 270 patients treated with IA thrombolysis. Futile recanalization was observed in 47 (49%). In univariate analysis, patients with futile recanalization were older (73 ± 11 versus 58 ± 15 years, P sup> .0001) and had higher median initial NIHSS scores (19 versus 14, P 70 years (OR, 4.4; 95% CI, 1.9–10.5; P = .0008) and initial NIHSS score 10–19 (OR, 3.8; 95% CI, 1.7–8.4; P = .001), and initial NIHSS score 20 (OR, 64.4; 95% CI, 28.8–144; P < .0001). CONCLUSIONS: Futile recanalization is a relatively common occurrence following endovascular treatment, particularly among elderly patients and those with severe neurologic deficits. Abbreviations: ACA, anterior cerebral artery • BA, basilar artery • CI, confidence interval • Gp IIb/IIIa, glycoprotein IIb/IIIa • h, hour • IA, intra-arterial • ICA, internal carotid artery • ICH, intracerebral hemorrhage • IMS, Interventional Management of Stroke • IV, intravenous • MCA, middle cerebral artery • MERCI, Mechanical Embolus Removal in Cerebral Ischemia • mRS, modified Rankin Scale • N/A, not applicable • NIHSS, National Institutes of Health Stroke Scale • NINDS, National Institute of Neurological Disorders and Stroke • OR, odds ratio • PCA, posterior cerebral artery • PROACT, Prolyse in Acute Cerebral Thromboembolism • rtPA, recombinant tissue plasminogen activator • TIMI, Thrombolysis in Myocardial Infarction • VA, vertebral artery The goal of IV and IA thrombolytic therapy in acute stroke is to recanalize an occluded vessel to salvage ischemic but still-viable brain tissue. Recanalization correlates with good clinical outcome in most, but not all, reported literature.1 Futile recanalization occurs when successful recanalization fails to improve the functional outcome. In the IMS II trial, 60% (33/55) of subjects treated with IA rtPA via the MicroLysUS infusion catheter (EKOS, Bothell, Washington) or standard microcatheters had partial or complete reperfusion (TIMI grade 2 and 3). Of those 33 subjects, 15 (55%) had a 3-month favorable outcome as measured by an mRS score of 0–2.2 Other major studies did not specifically report the rate of futile recanalization. Yet, there was always a mismatch between recanalization and favorable outcome rates, suggesting that futile recanalization occurs in variable proportions regardless of treatment strategy. In the PROACT II trial,3 the recanalization rate was 66%, while the rate of favorable outcome was 40% (26% mismatch). A similar pattern was documented in the Combined Lysis of Thrombus in Brain Ischemia by Using Transcranial Sonography and Systemic TPA trial (82% recanalization, 51% favorable outcome),4 the MERCI trial (68% recanalization rate, 34% favorable outcome),5,6 and the Multi MERCI trial (68% recanalization rate, 32% favorable outcome).7 Given the resources required for and risk associated with endovascular treatment,8–10 it is important to identify the subset of patients who will not benefit from recanalization. The aim of our study was to assess the rate of and factors associated with futile recanalization following endovascular treatment among patients with acute ischemic stroke. Materials and Methods We combined individual patient data from 6 studies of patients treated with IA thrombolysis in the setting of acute ischemic stroke. All studies were approved by local institutional review boards. The methodology and results of all 6 studies as well as the compilation and patient selection process for current analysis are summarized in On-line Tables 1–3, respectively. Study A. Study A prospectively evaluated the safety of mechanical disruption of thrombus following a full dose of IV rtPA in the setting of acute stroke within 3 hours of symptom onset. Favorable outcome (1–3 months; mRS score, 2) was determined by either a clinic visit or a telephone interview.11 Study B. Study B was a prospective nonrandomized open-label trial aimed at evaluating the safety of IA reteplase in conjunction with IV abciximab in patients with acute ischemic stroke presenting 3–6 hours after symptom onset. The primary end point was symptomatic ICH at 24–72 hours, and secondary end points were partial or complete recanalization, early neurologic improvement at 24 hours, and favorable outcome at 1 month (mRS score, 2). The study was approved by the US Food and Drug Administration and was overseen by an independent data and safety monitoring board.12 Study C. Study C prospectively evaluated the safety of the MicroLysUS infusion catheter (EKOS) (a standard microinfusion catheter with a ring sonography transducer tip) for acute embolic stroke treatment. The secondary goal was to assess the efficacy of sonography-accelerated thrombolysis in improving clinical outcomes.13 Study D. Study D retrospectively assessed the rate of reocclusion and its effect on clinical outcome after IA thrombolysis for acute ischemic stroke. Favorable outcome (1–3 months; mRS score, 2) was determined by either a clinic visit or a telephone interview.14 Study E. Study E was a case series of consecutive patients who presented to an academic center with ischemic stroke, had angiographically confirmed arterial occlusion, and were treated with IA thrombolysis. Favorable outcome (1–3 months; mRS score, 2) was determined by either a clinic visit or a telephone interview.15 Study F. Study F was a case series representing the experience of another academic center. Consecutive patients with acute ischemic stroke treated with IA thrombolysis were included. Functional outcome was assessed 3 months after the index event by using the mRS. Several articles have been published on the basis of these data.16–20 In each of the 6 studies, neurologic evaluation including the NIHSS score was documented before the procedure, 24 hours after the procedure, and on day 7 or discharge. Radiologic evaluation with CT scan of the head was performed before the procedure and 24–48 hours after. CT scan was also performed whenever neurologic deterioration occurred. Angiographic occlusion and recanalization were classified by interventional neurologists or neuroradiologists by using either the TIMI grading scale21 or the Qureshi grading scale.22 The TIMI is a point scale from 0 (complete occlusion) to 3 (complete recanalization), which was originally developed to assess arterial occlusion and perfusion in patients with myocardial infarction and was later adopted for use in stroke by the PROACT II trial.2 The TIMI grading system does not account for occlusion location or collateral circulation. The Qureshi grading system is a scale from 0 (best possible score) to 5 (worst possible score), which angiographically classifies arterial occlusion and recanalization. The Qureshi grading system was specifically designed for ischemic stroke to address the limitations of the pre-existing TIMI grading system. The Qureshi grading scale has been validated for use in acute stroke (Table 1).22,23 Complete recanalization was defined by a posttreatment TIMI grade of 3,24 which is equivalent to a Thrombolysis in Cerebral Infarction reperfusion grade of 3.25 Six patients did not have a posttreatment TIMI grade available. In those patients, complete recanalization was defined as a Qureshi grade22 of 0. All 3 grades represent complete patency with filling of all distal branches. A distinct parameter for recanalization of the primary arterial occlusive lesion independent of global reperfusion24,25 was not collected. Favorable outcome was defined as mRS26–28 2 at 1–3 months. "Futile recanalization" was defined as unfavorable outcome despite complete recanalization. View this table: [in this window] [in a new window] Table 1: Qureshi grading scheme for stratification of patients with acute ischemic stroke based on initial site of occlusion and collateral supply Statistical Analysis Patient characteristics were descriptively compared across studies. The study sample was dichotomized on the basis of favorable outcome into futile and nonfutile recanalization groups. Univariate analysis was performed to compare the 2 groups with respect to demographic, clinical, and radiologic variables, as well as rates of outcome events. The exact 2 test was used for categoric data; analysis of variance, for continuous data; and the Kruskal-Wallis test, for nonparametric variables. We performed the test for heterogeneity to identify the possibility of 1 study skewing the results of the combined analysis. There was statistically significant heterogeneity between the studies. Multivariate analysis was performed to study predictors of futile recanalization by using the generalized linear model with logit link, which takes into account the structure of the data (patients within study) and provides more conservative estimates of association. Variables selected for the multivariate analysis were age, initial NIHSS score, initial severity of arterial occlusion defined by Qureshi grade, and time to treatment. Selection was based on clinical rather than statistical significance. A test for interaction was performed for statistically significant main effect predictors. A P value 10. In the NINDS trial, all age groups benefited from treatment, but patients <75 years of age and patients with an NIHSS score of 68 years and NIHSS score of <20 were predictors of good outcome in multivariate analysis.30 Other case series reported age <60 years and NIHSS score of 2 have been consistently used to define poor outcomes in trials evaluating endovascular treatment in patients with acute ischemic stroke.2,4 Finally, the findings on the initial CT scan, which is an important factor in clinical decision making, were not collected consistently and, therefore, are not included in the present analysis. Serial diffusion and perfusion MR imaging data were not available, which would have allowed us to mechanistically define the role of microvascular compromise and reocclusion. While there is a possibility that the quantitative estimates of futility may have been different with greater standardization, we do not think that the basic findings of the study would have been affected. Conclusions In a large pooled analysis, we observed that futile recanalization is a relatively common occurrence following endovascular treatment, particularly among elderly patients and those with severe neurologic deficits. Further studies need to explore the mechanisms underlying futile recanalization and develop methods to effectively exclude such patients from receiving endovascular treatment in various protocols.