Futile Recanalization in Mechanical Embolectomy Trials

Abstract

See related article, pages 953-960. I t is well known that clot burden is likely a major determinant of vessel recanalization rates with the volume of thrombus to be dissolved by fibrinolytic agents much larger in the intracranial carotid artery than in the middle cerebral artery. So, the more distal the occlusion is located, the higher the likelihood of recanalization. This statement seems to be true for intravenous thrombolysis as demonstrated in several transcranial Doppler studies showing that the probability of complete recanalization at 2 hours of tissue plasminogen activator (tPA) bolus is 44%, 29%, and 10% in the distal middle cerebral artery, proximal middle cerebral artery, and terminal internal carotid artery, respectively. 1 However, a differential treatment response according to clot size and location has not been demonstrated in patients with stroke undergoing mechanical embolectomy. Several methodologi-cal, technical, and pathophysiological differences preclude the translation of this "clot-burden effect" of intravenous tPA therapy into mechanical revascularization trials. In this issue of Stroke, Shi et al 2 retrospectively analyzed the pooled data of patients with middle cerebral artery strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patients were dichoto-mized into 2 groups: middle cerebral artery M1 occlusions and isolated M2 occlusions. Baseline characteristics, revas-cularization rates, hemorrhage rates, complications, outcomes , and mortality were evaluated for both groups. The authors observed that patients with isolated M2 occlusions were revascularized at a higher rate (82.1% versus 60%), required fewer number of passes, and were associated with a trend of a shorter median procedure time than patients with M1 occlusions. However, no statistically significant differences were found between the M2 and M1 groups for favorable 90-day outcome (modified Rankin Scale0 to 2; 40.7% versus 33.3%) or 90-day mortality (25.9% versus 32.9%). Although clot burden may represent a major determinant of revascularization success, other factors different than a smaller clot size may influence the higher recanalization rates seen in M2 compared with M1 occlusions. In the study by Shi et al, the mean onset-to-groin puncture time was 4.5 hours. So, the angiographic identification of a M2 clot may represent an advanced ongoing stage of M1 recanalization, particularly in those patients pretreated with intravenous tPA. In fact, Shi et al observed that recanalization rates at the end of the procedure were higher in patients who were pretreated with tPA. This finding raises the hypothesis that pretreatment with tPA may soften the clot favoring catheter penetration and retrieval. Moreover, M2 clots may have a better collateral blood supply and larger areas of clot-in 2 fronts of recana-lization-exposed to circulating tPA. On the other hand, most patients with M2 occlusion were included in the Multi MERCI trial, so the higher recanalization rates in the M2 occlusion group may result from an incorporation of knowledge gained from the practitioner's increasing experiences and the newer generation of Merci Retriever devices available in Multi MERCI. Angiographic studies have elucidated the relationship between the location of arterial occlusion and outcome after intravenous thrombolysis. 3 Furthermore, transcranial Doppler studies have shown that M2 recanalization increases 2-fold the likelihood of a good outcome compared with M1 recan-alization. 2 In contrast, the pooled analysis of Merci in Multi MERCI shows that despite the higher recanalization rates in M2 occlusions, short-and long-term outcomes were comparable to M1 occlusions. Although the lack of differences in clinical outcome may be due to a statistical Type II error because the sample size of patients with M2 occlusion enrolled into these 2 trials was smaller than that of the patients with M1 occlusion, a proportion of patients with M2 occlusion may have experienced nonnutritional or futile recanalization. Futile recanalization occurs when successful recanalization fails to improve the functional outcome. In the Interventional Management of Stroke II trial, 45% of subjects who achieve partial or complete reperfusion (Thrombolysis In Myocardial Ischemia Grade 2 and 3) had a poor 3-month outcome (modified Rankin Scale score 3). In the Pro-Urokinase for Acute Cerebral Thromboembolism II trial, the mismatch between recanalization and favorable outcome was 26%. Similarly, in the Combined Lysis of Thrombus in Brain Ischemia by Using Transcranial Sonography and Systemic TPA trial, the rate of futile recanalization was 31% (82% recanalization, 51% favorable outcome), the MERCI trial 34%, and the Multi MERCI trial 36% (68% recanalization rate, 32% favorable outcome). In a recent multicenter study, Hussein et al 4 observed futile recanalization in 49% of patients who received endovascular treatment for acute ische-mic stroke. In this study, age 70 years (OR, 4.4; 95% CI, 1.9 to 10.5) and initial National Institutes of Health Stroke