Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion

Abstract

ImportancePrior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection.ObjectiveTo evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection.Design, Setting, and ParticipantsThis was a randomized, open-label, outcome assessor–blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020).InterventionsEC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control.Main Outcomes and MeasuresThe primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years.ResultsAmong 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, −3.6% [95% CI, −10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, −5.4% [95% CI, −12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, −0.2% to 4.0%]; P = .08).Conclusions and RelevanceAmong patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years.Trial RegistrationClinicalTrials.gov Identifier: NCT01758614

Extracranial-Intracranial Bypass in Patients With Symptomatic Artery Occlusion

“…Thus, we disagree with this study’s statement that “the findings do not support the addition of EC-IC bypass surgery to medical therapy for the treatment of patients with symptomatic atherosclerotic occlusion of the [internal carotid artery] or [middle cerebral artery].” In our view, the meaning of the trial would have been better conveyed by stating that EC-IC bypass carries a 30-day risk of stroke or death of 6.2%, but subsequently confers superior protection against ischemic stroke than medical management alone. The meaning of an exploratory trial performed in patients from China treated by selected expert surgeons in principle is not generalizable.…”

“…To the Editor We disagree with the analysis and interpretation of the recent Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS) that compared medical management and extracranial-intracranial (EC-IC) bypass with medical management alone . Given the nature of this trial, which was designed to test whether an immediate surgical risk to prevent future strokes would benefit patients with intracranial arterial occlusion, the use of a Cox proportional hazards model for time-to-event analyses was certain, a priori, to violate the proportional hazard assumption, as the authors realized after the fact.…”

Future of Endovascular and Surgical Treatments of Atherosclerotic Intracranial Stenosis

“…CMOSS examined direct bypass for symptomatic ICA or MCA occlusion with hemodynamic insufficiency and again failed to demonstrate evidence of benefit in the surgical intervention group. 63…”

Predicting Stroke Recurrence in Occlusive Disease Using Noninvasive Quantitative Mapping of Cerebrovascular Reserve

“…Prospective studies have documented that the presence of impaired hemodynamics, and particularly of misery perfusion, carries a 4-to 12-fold higher risk of ipsilateral ischemic stroke recurrence despite best medical management. [7][8][9] This has been the rationale behind the randomized trials of extracranial-intracranial arterial bypass, which, despite multiple reports of benefit in individual patients, [10][11][12] have so far been neutral largely because of a high periprocedural risk of stroke, [13][14][15] the mechanisms of which are still incompletely elucidated. Pending new trials with improved patient selection and surgical technique, extracranialintracranial bypass is occasionally carried out as a last resort in cases of recurrent stroke despite best medical management, which should include appropriate use of antithrombotics given the likely compounding role of distal microemboli in a good fraction of hemodynamic strokes/TIAs.…”