Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Aug 22;330(8):704-714.
doi: 10.1001/jama.2023.13390.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial

Yan Ma  1 , Tao Wang  1 , Haibo Wang  2   3 , Sepideh Amin-Hanjani  4 , Xiaoguang Tong  5 , Jiyue Wang  6 , Zhiyong Tong  7 , Dong Kuai  8 , Yiling Cai  9 , Jun Ren  10 , Donghai Wang  11   12 , Lian Duan  13 , Aisha Maimaitili  14 , Chunhua Hang  15 , Jiasheng Yu  16 , Xuesong Bai  1 , William J Powers  17 , Colin P Derdeyn  18 , Yangfeng Wu  2 , Feng Ling  19 , Yuxiang Gu  20 , Liqun Jiao  19 ; CMOSS Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial

Yan Ma et al. JAMA. .

Abstract

Importance: Prior 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.

Objective: To 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 participants: This 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).

Interventions: EC-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 measures: The 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.

Results: Among 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 relevance: Among 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 registration: ClinicalTrials.gov Identifier: NCT01758614.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Derdeyn reported receiving personal fees from Penumbra (data and safety monitoring board for MIND and THUNDER trials), NoNo Inc (data and safety monitoring board for ESCAPE NEXT and FRONTIER trials), and Euphrates Vascular Inc and grants from Siemens Healthineers outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Enrollment and Follow-Up in the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS) Trial
ICA indicates internal carotid artery; MCA, middle cerebral artery; and TIA, transient ischemic attack. aSimple randomization without block or stratification. bMajor protocol violation due to baseline modified Rankin Scale score of 4.
Figure 2.
Figure 2.. Cumulative Probability of the Primary Outcome, According to Treatment Assignment
The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. Nine patients lost to follow-up within 2 years in the surgical group and 6 patients in the medical group were treated as censored data. All other patients were followed up to event or 2 years. The median time of observation was 24.0 months (IQR, 24.0-24.0) for the surgical group and 24.0 months (IQR, 24.0-24.0) for the medical group. P = .39 for log-rank testing between the surgical group and medical group with the center information (site effect) as a stratification factor. The shading indicates 95% CI of the primary outcome.
Figure 3.
Figure 3.. Post Hoc Subgroup Analysis for the Primary Outcomea
HR indicates hazard ratio; and TIA, transient ischemic attack. aThe primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. bMean transit time designates the mean time required for a contrast bolus to traverse the voxel and is measured in seconds. Mean transit time is inversely proportional to cerebral perfusion pressure and prolonged value indicates arterial stenosis or occlusion. cCerebral blood flow refers to the volume of blood flowing in a unit of brain mass during a unit of time (measured in mL/100 g/min). Relative cerebral blood flow denotes symptomatic side/asymptomatic side.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. White H, Boden-Albala B, Wang C, et al. . Ischemic stroke subtype incidence among Whites, Blacks, and Hispanics: the Northern Manhattan Study. Circulation. 2005;111(10):1327-1331. doi:10.1161/01.CIR.0000157736.19739.D0 - DOI - PubMed
    1. Wang Y, Zhao X, Liu L, et al. ; CICAS Study Group . Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: the Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke. 2014;45(3):663-669. doi:10.1161/STROKEAHA.113.003508 - DOI - PubMed
    1. Grubb RL Jr, Derdeyn CP, Fritsch SM, et al. . Importance of hemodynamic factors in the prognosis of symptomatic carotid occlusion. JAMA. 1998;280(12):1055-1060. doi:10.1001/jama.280.12.1055 - DOI - PubMed
    1. Kern R, Steinke W, Daffertshofer M, Prager R, Hennerici M. Stroke recurrences in patients with symptomatic vs asymptomatic middle cerebral artery disease. Neurology. 2005;65(6):859-864. doi:10.1212/01.wnl.0000175983.76110.59 - DOI - PubMed
    1. Flaherty ML, Flemming KD, McClelland R, Jorgensen NW, Brown RD Jr. Population-based study of symptomatic internal carotid artery occlusion: incidence and long-term follow-up. Stroke. 2004;35(8):e349-e352. doi:10.1161/01.STR.0000135024.54608.3f - DOI - PubMed

Publication types

MeSH terms

Substances

Associated data