In CREST-2, carotid artery stenting added to intensive medical therapy significantly reduced the composite of perioperative stroke or death or ipsilateral stroke through four years versus intensive medical therapy alone in patients with high-grade asymptomatic carotid stenosis. In the trial’s parallel surgical arm, carotid endarterectomy plus intensive medical therapy did not achieve a significant benefit over medical therapy alone on the same endpoint. The two NIH-sponsored, observer-blinded trials enrolled 1,245 patients in the stenting arm and 1,240 in the endarterectomy arm and were presented at SVIN and VEITH with simultaneous publication in the New England Journal of Medicine.
The immediate news is twofold: definitive, randomized evidence now supports carotid stenting as beneficial on top of contemporary medical therapy in asymptomatic severe stenosis, and endarterectomy did not show a statistically significant advantage in its parallel comparison. Separately, device maker InspireMD, which markets the CGuard Prime stent, is positioning itself to capitalize on any procedural shift, pointing to its C-GUARDIANS pivotal data showing a 1.93% major adverse event rate at 12 months in high surgical risk patients. CREST-2 was not funded by InspireMD and did not evaluate a specific device.
Strategically, the alignment is clear. After a decade in which guideline momentum and payer policy trended toward medical management for asymptomatic disease, a positive randomized stenting signal reopens procedural growth in a segment that had been largely stagnant outside of high-risk subsets. InspireMD’s move is an expansion play aimed at category validation rather than product-specific differentiation: if the class wins, vendors with clean safety signals and operationally simple systems stand to gain share. The more surprising comparative outcome—stenting benefiting where endarterectomy did not—will invite interrogation of device generations, operator credentialing, perioperative management, and the intensity of risk factor control across arms. But even amid scrutiny, the directional takeaway favors an endovascular-first posture.
For sites, the implications are immediate. Neurointerventional and vascular programs can anticipate renewed referral flow for asymptomatic high-grade lesions, prompting capacity planning around cath lab time, embolic protection inventory, antiplatelet management protocols, and post-procedure monitoring pathways that enable same-day or next-day discharge. Credentialing committees and quality leaders will revisit operator volume thresholds and complication tracking, likely anchoring to SVS VQI or comparable registries as payers demand real-world performance that mirrors trial-era event rates. Sponsors and device manufacturers will accelerate post-market and registry strategies to map CREST-2’s class-level effect to specific platforms, anticipating payer and guideline requests for device-level evidence. Regulators and CMS face pressure to reconcile historic coverage restrictions for stenting—especially in asymptomatic patients—with a new randomized signal; any NCD update would materially change adoption curves. CROs supporting carotid programs may see increased demand for pragmatic trials, cost-effectiveness analyses, and subgroup work in diabetics, women, the very elderly, and patients with contralateral occlusion or tandem disease.
The next phase hinges on details not yet widely digested: absolute event rates, hazard ratios by age and sex, perioperative complication profiles, antiplatelet adherence, and operator experience gradients. Guideline committees from vascular surgery, neurology, and cardiology will need to harmonize recommendations, and CMS will determine whether coverage broadens beyond high surgical risk. Expect near-term jockeying among stent vendors to link platform features to embolic durability and microembolization control, alongside site-level pushes to standardize imaging-driven selection and discharge pathways. The risk is straightforward: if real-world outcomes drift above trial-era thresholds or if the absolute risk reduction proves modest in lower-risk subgroups, payers and hospitals may blunt broad uptake. Watch for guideline updates, a CMS NCD reconsideration, device-specific registry outputs, and whether centers pivot referral patterns from endarterectomy to stenting as the evidence migrates from podium to practice.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
