Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial

Abstract

Context: Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically.

Objective: To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia.

Design: Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010.

Setting: Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers.

Participants: Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events.

Interventions: Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants.

Main outcome measure: For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization.

Results: The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, -10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%).

Conclusion: Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years.

Trial registration: clinicaltrials.gov Identifier: NCT00029146.

Figure 1

Trial Flow Diagram. The most common reasons recorded for failure of screened participants to meet clinical eligibility criteria were transient ischemic attack or stroke not in territory of occluded carotid artery (1597), transient ischemic attack or stroke not within 120 days (485), language comprehension not intact (283), non-atherosclerotic condition causing carotid artery occlusion (280), modified Barthel index not ≥ 12/20 (168), unsuitable surgical candidate (160), no occlusion of 1 internal carotid artery (114), not competent to give informed consent (110), subsequent surgery planned that might alter cerebral hemodynamics (105), age not 18–85 (104). For each screened participant, only 1 reason needed to be provided.

Figure 2

Kaplan-Meier cumulative failure curves for the intention-to-treat analysis of the primary end point. The primary endpoint is defined in the footnote to Table 3. The number of participants who remained event free and available for follow-up evaluation at each 90 day interval is shown in the appropriate color for each group at the bottom of the graph.