Transfemoral stenting for severe carotid stenosis in addition to intensive medical management halved the risk of stroke and death over 4 years, and reduced post-procedural stroke risk by 75%, the CREST-2 study found. Endarterectomy, however, did not show a significant benefit over medical therapy alone. Gary Roubin, MD, PhD, Cardiovascular Associates of the Southeast in Birmingham, Alabama, presented the results at a late-breaking clinical trials session on Tuesday at the Cardiovascular Research Technologies (CRT) 2026 meeting in Washington, D.C. Despite many carotid disease patients currently under cardiologist care, the best approach for severe asymptomatic carotid stenosis has remained elusive, the investigators said. CREST-2 was therefore set up as two concurrent multicenter, randomized, observer-blinded trials enrolling a total 2,485 patients with ≥70% asymptomatic carotid stenosis across North America, Australia, Israel and Spain. One compared medical therapy alone to carotid artery stenting (CAS) plus medical therapy (1,245 patients split 629 to medical therapy alone and 616 to CAS + medicine), while the other compared medical therapy alone to endarterectomy (CEA) plus medical therapy (1,240 patients split 623 patients to medical therapy alone and 617 to CEA). At baseline, the endarterectomy similarly aged (a mean of 70.4+7.6 on medicine alone and 70.7+7.8 on medicine + CEA in the endarterectomy trial vs 69.7+7.7 and 69.3+8.1, respectively in CAS), similarly sex-weighted (majority men) and had similar rates of hypertension (84.9% on medicine alone and 85.1% on medicine + CEA in the endarterectomy trial vs 87.4% and 88%,r respectively in CAS). Diabetes was present for 38% in medicine alone and 34.4% in medicine + CEA in the endarterectomy trial vs 37,8% and 40.7%, respectively in the CAS trial, while dyslipidemia was present in 90% and 91.5%, respectively in CEA and 93.3% and 92% in CAS. Patients had no history of stroke or ipsilateral transient ischemic attack (TIA) to the stenosis within 180 days of randomization, those with lesions >2cm were excluded, as were those with circumferential calcification, severe tortuosity, type III aortic arch, severe therosclerotic arch and common carotid. Diagnoses of ≥70 % carotid stenosis were determined by North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, though patient selection was left to operator discretion, Roubin noted. There was no screening committee process, and “credentialing of interventionists and surgeons was based on competency metrics not necessarily requiring extensive experience,” according to the abstract. Of the 228 interventionists credentialled, over 40% were interventional cardiologists. All U.S. Food and Drug Administration (FDA)-approved stents and EPD systems were allowed at the operator’s discretion, while closed cell stents were encouraged Results The main outcome was stroke or death within 44 days, or ipsilateral stroke up to four years. In the CAS trial, it occurred for 2.8% (95% confidence interval [CI]: 1.5% to 2.8%) of stented patients vs 6% (95% CI: 3.8% to 8.3%) of those on medical therapy alone (p = 0.016). In the endarterectomy trial, the endpoint occurred in 3.7% of those on CEA + medical therapy (95% CI: 2.1% to 5.5%) vs 5.3% (95% CI: 3.3% to 7.4%) for medical therapy alone (p = 0.24). Peri-procedural outcomes between 0 – 44 days included stroke and death, a rate of 1.3% (95% CI, 0.6% to 2.5%) for stenting and 1.5% (95% CI: 0.7% to 2.8%) for endarterectomy. In the CAS trial, the annual stroke risk post procedure was 0.4% (95% CI: 0.2% to 0.9%) for stenting and 1.7% (95% CI: 1.1% to 2.4%) for medical therapy alone, making the relative risk 4.07 times (95% CI: 1.1 to 2.4) lower for stenting, the researchers noted in the abstract. Meanwhile in the CEA trial, annual stroke risk post procedure was 0.5% (95% CI: 0.3% to 1.0%) for endarterectomy and 1.3% (0.9% to 2.0%) and for medical therapy alone, a relative risk 2.3 times (95% CI: 1.13 to 5.00) lower for endarterectomy. At 4 years, the absolute risk difference of any perioperative stroke or death plus ipsilateral stroke thereafter was 3.2% higher for medicine alone vs CAS + medicine in the stenting study (6% medicine alone vs 2.8% CAS + medicine; 95% CI: 0.6 to 5.9; p = 0.016). The 4-year result in the endarterectomy trial showed an absolute risk difference of 1.6% in favour of CEA + medicine (5.3% medicine alone vs 3.7% CEA + medicine; 95% CI: -1.1 to 4.3; p = 0.24). Overall, CAS carried half the risk of intensive medical management alone (2.8% vs 6%; absolute risk difference: 3.2; 95% CI: 0.6 to 5.9; p = 0.016), said Roubin. CAS ‘prevents strokes’ Individually, stroke risk post-procedurally was cut from 1.7% to 0.4% with CAS, said Dr. Roubin. “The results of this rigorous trial are translatable to general clinical practice providing stenting operators practice competent stenting in appropriately selected patients,” Dr. Roubin concluded. Image Credit: Bailey G. Salimes, CRTonline.org Image Caption: Gary S. Roubin, MD, PhD, presents his late-breaking clinical trial at Cardiovascular Research Technologies (CRT) 2026 in Washington, D.C.