The Carotid and Middle Cerebral Artery Occlusion Surgery Study

Summary

The recently published Carotid Occlusion Surgery Study (COSS) failed to show a benefit of extracranial-intracranial (EC-IC) bypass surgery over medical therapy in patients with symptomatic hemodynamically significant carotid occlusion. Since then on, different controversies have been raised on several aspects including the study population, qualifications of surgeons and hemodynamic evaluation. In COSS protocol, the primary inclusion population is the patient demonstrating occlusion of unilateral ICA while the contralateral ICA less than 50% stenosis. Because of the enrollment problems, in the final result report, 18% patients suffered from contralateral ICA stenosis more than 50%. As we known, COSS utilized oxygen extraction fraction (OEF) ratio by PET as the criterion of hemodynamic evaluation. Bilateral ICAs lesion will disturbed the ratio even the identifying the subgroup of patients with hemodynamic insufficiency. As an interventional trial, the COSS should ensure the certification for the experienced surgeons. While for expanding the number of centers and enhancing recruitment, COSS made some concessions on the surgeons training and certification. The 15% postoperative event rate is not the best that can be achieved according to recent surgical technical development. The cerebral hemodynamic insufficiency has been considered as the primary pathophysiological factor for patients with ICA or MCA occlusion. For these patients, antiplatelet therapy is not likely to prevent hemodynamic stroke.EC-IC bypass surgery probably will be the possible effective therapy. These underlying assumptions deserved further exploration and more strict research.So the CMOSS study in China is designed to compare the efficacy and safety of EC-IC bypass surgery with medical therapy in patients with symptomatic hemodynamically significant carotid occlusion.

Timeline

Start

2013-06-06

Primary completion

2018-03-02

Completion

2020-03-01

Publications

• Results Powers WJ, Clarke WR, Grubb RL Jr, Videen TO, Adams HP Jr, Derdeyn CP; COSS Investigators. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA. 2011 Nov 9;306(18):1983-92. doi: 10.1001/jama.2011.1610.
• Results Carlson AP, Yonas H, Chang YF, Nemoto EM. Failure of cerebral hemodynamic selection in general or of specific positron emission tomography methodology?: Carotid Occlusion Surgery Study (COSS). Stroke. 2011 Dec;42(12):3637-9. doi: 10.1161/STROKEAHA.111.627745. Epub 2011 Sep 29.
• Results Amin-Hanjani S, Barker FG 2nd, Charbel FT, Connolly ES Jr, Morcos JJ, Thompson BG; Cerebrovascular Section of the American Association of Neurological Surgeons; Congress of Neurological Surgeons. Extracranial-intracranial bypass for stroke-is this the end of the line or a bump in the road? Neurosurgery. 2012 Sep;71(3):557-61. doi: 10.1227/NEU.0b013e3182621488.
• Results Grubb RL Jr, Derdeyn CP, Fritsch SM, Carpenter DA, Yundt KD, Videen TO, Spitznagel EL, Powers WJ. Importance of hemodynamic factors in the prognosis of symptomatic carotid occlusion. JAMA. 1998 Sep 23-30;280(12):1055-60. doi: 10.1001/jama.280.12.1055.
• Results Waaijer A, van der Schaaf IC, Velthuis BK, Quist M, van Osch MJ, Vonken EP, van Leeuwen MS, Prokop M. Reproducibility of quantitative CT brain perfusion measurements in patients with symptomatic unilateral carotid artery stenosis. AJNR Am J Neuroradiol. 2007 May;28(5):927-32.
• Wang T, Yang Y, Wang H, Liu D, Wang J, Luo J, Yang R, Li T, Gong H, Sun X, Derdeyn CP, Ma Y, Jiao L; CMOSS Investigators. CT Perfusion for Predicting Ischemic Stroke in Patients With Symptomatic Carotid or Middle Cerebral Artery Occlusion: A Post Hoc Analysis of the CMOSS Study. Stroke. 2025 Sep;56(9):2579-2587. doi: 10.1161/STROKEAHA.125.051352. Epub 2025 Jun 19.
• Li X, Li Y, Wang T, Sun X, Lu G, Xu X, Yang R, Luo J, Bai X, Tong X, Gu Y, Wang J, Tong Z, Wang Y, Cai Y, Ren J, Wang D, Duan L, Maimaitili A, Hang C, Yu J, Chen T, Ma Y, Jiao L; CMOSS Investigators. Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial. Stroke. 2025 Feb;56(2):362-370. doi: 10.1161/STROKEAHA.124.048766. Epub 2024 Dec 27.
• Lu G, Wang T, Sun X, Yang R, Luo J, Tong X, Gu Y, Wang J, Tong Z, Kuai D, Cai Y, Ren J, Wang D, Duan L, Maimaitili A, Hang C, Yu J, Ma Y, Liu S, Jiao L; for CMOSS investigators. Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS. J Am Heart Assoc. 2024 Jul 2;13(13):e034056. doi: 10.1161/JAHA.123.034056. Epub 2024 Jun 27.
• Ma Y, Wang T, Wang H, Amin-Hanjani S, Tong X, Wang J, Tong Z, Kuai D, Cai Y, Ren J, Wang D, Duan L, Maimaitili A, Hang C, Yu J, Bai X, Powers WJ, Derdeyn CP, Wu Y, Ling F, Gu Y, Jiao L; CMOSS Investigators. Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial. JAMA. 2023 Aug 22;330(8):704-714. doi: 10.1001/jama.2023.13390.
• Ma Y, Gu Y, Tong X, Wang J, Kuai D, Wang D, Ren J, Duan L, Maimaiti A, Cai Y, Huang Y, Wang X, Cao Y, You C, Yu J, Jiao L, Ling F. The Carotid and Middle cerebral artery Occlusion Surgery Study (CMOSS): a study protocol for a randomised controlled trial. Trials. 2016 Nov 16;17(1):544. doi: 10.1186/s13063-016-1600-1.

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