The initial findings from a recent randomised controlled trial (RCT) do not support the addition of extracranial to intracranial (EC-IC) bypass surgery to the current medical management of patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusions. Tao Wang (Xuanwu Hospital, Beijing, China) delivered these results at the International Stroke Conference (ISC; 8–10 February 2023, Dallas, USA).
Outlining the backdrop to the CMOSS trial, Wang cited mixed results in previous studies in this space—including COSS, which produced largely negative bypass surgery results and was terminated early for futility, and the Japanese EC-IC Bypass trial, from which the final results were never published in spite of interim analyses indicating potential benefits with bypass surgery.
The CMOSS study, Wang continued, was therefore set up to compare EC-IC bypass surgery plus medical therapy with medical therapy alone in preventing stroke/death in symptomatic stroke patients with ICA or MCA occlusion, and haemodynamic insufficiency, in a Chinese population.
The trial—a multicentre, open-label RCT conducted across 13 tertiary care centres in China—also featured refined patient selection and operator experience, Wang noted. Its primary endpoint was a composite of any stroke of death within 30 days, or ischaemic stroke in the territory of a qualifying artery beyond 30 days through two years after randomisation. Secondary endpoints included disabling/fatal stroke, transient ischaemic attack (TIA), and National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores, as well as complications associated with the surgical procedures.
Following enrolment and 1:1 randomisation to either EC-IC bypass surgery plus medical therapy, or medical therapy alone, a total of 161 patients (mean age=52 years, 77.6% male) were included in the surgical group and 163 patients (mean age=53.5 years, 81% male) were included in the medical group for the intention-to-treat analysis. Wang stated that the baseline characteristics between the two groups were essentially equal but that, compared to COSS, CMOSS patients had a lower average age and a lower proportion of stroke as their qualifying event.
Regarding the trial’s primary outcome measure, Wang reported that 13 patients (8.6%) in the surgical group and 19 patients (12.3%) in the medical group experienced an event, and there was therefore no significant difference between the two groups. A post-hoc analysis also revealed no significant differences in stroke/death rates within 30 days, although there was a significantly lower rate of ipsilateral ischaemic stroke beyond 30 days in the surgical group (2% vs 10.3% in the medical group).
Wang went on to inform the ISC audience that there were no significant differences observed regarding any of the secondary outcomes. In total, six complications adjudged to have been linked to the procedures (4%) occurred in the surgical group.
The investigators conducted post-hoc subgroup analyses across multiple “important factors”, according to Wang. For example, potential benefits favouring bypass surgery versus medical therapy in MCA occlusions, and in cases of severe haemodynamic insufficiency, were observed—and these results “give us some suggestions for future studies”.
Another finding highlighted by Wang was the improved overall efficacy in the medical therapy group of CMOSS, as compared to COSS, as 12.3% of patients reached the former’s main efficacy endpoint, while 21% did so in the latter trial. The speaker attributed this to a younger, lower-risk patient population in CMOSS, as well as better control of risk factors.
Furthermore, the perioperative stroke rate in CMOSS (6.2%) was “substantially lower” than in prior studies—15% in COSS and 12% in EC-IC Bypass. Wang said this was due to CMOSS adopting stricter criteria for surgeon certification than COSS, and enforcing stricter perioperative management as well.
After referencing its potential limitations—including a lack of sham surgery creating the scope for bias at individual centres, and “uncertain” generalisability of the results to populations outside of China—Wang concluded that CMOSS’ findings do not support the addition of EC-IC bypass surgery to current medical therapy in symptomatic ICA/MCA occlusion patients.
However, the speaker ended his presentation on a more positive note, suggesting that the overall efficacy of both bypass surgery and medical therapy in these patients have “improved simultaneously”. One promising direction for the future, he added, may be to assess the benefits of bypass surgery versus medical therapy in more specific patient populations.