Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial

Abstract

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

Methods: A post hoc analysis was performed of the CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study), which was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China between June 2013 and March 2018. A total of 324 patients with internal carotid artery or middle cerebral artery occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency were randomized into a surgical group (n=161) that underwent EC-IC bypass surgery with medical therapy, and a medical group (n=163) that received antiplatelet therapy and stroke risk factor control alone. The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days up to 2 years after randomization. Receiver operating characteristic curves were drawn to explore the optimal age boundary, and survival analyses were used to explore differences between groups.

Results: Among the 324 patients (median age, 52.7 years; 79.3% men), an age cutoff of 55.5 years predicted the primary outcome in the surgical group (area under the curve, 0.649 [95% CI, 0.530-0.769]). Patients were further divided into an older group (>55.5 years) and a younger group (≤55.5 years). Younger patients who underwent bypass surgery showed a lower risk of the primary outcome (log-rank P=0.001) than older patients. Patients who underwent EC-IC bypass surgery had a lower risk than patients with medical therapy alone in the younger group (3.2% versus 11.6%; hazard ratio, 0.255 [95% CI, 0.071-0.916]; P=0.036), but not in the older group (17.5% versus 13.3%; adjusted hazard ratio, 0.597 [95% CI, 0.225-1.580]; P=0.298).

Conclusions: In patients aged 55.5 years or younger with symptomatic atherosclerotic occlusion of the internal carotid artery or middle cerebral artery and hemodynamic insufficiency, the addition of EC-IC bypass surgery to medical therapy significantly improved prognosis. These findings suggest that the clinical application of EC-IC bypass surgery needs more research to explore refined patient selection criteria incorporating more clinical features.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Keywords: atherosclerosis; hemodynamics; ischemic stroke; middle cerebral artery; stroke.