A score system to determine the five-year survival in patients with asymptomatic carotid stenosis under best medical therapy: results from the CARAS study

INTRODUCTION: Current international guidelines do not recommend carotid revascularization in patients with asymptomatic carotid artery stenosis (ACAS) with a life expectancy less than 5 years or high-risk clinical conditions. However, improvements in medical therapy leading to a reduction of cerebral ischemic events (CIEs) risk may improve long-term survival. After a previous report of 5-year CIE outcomes in a prospective observational study of ACAS patients treated with best medical therapy (BMT), the long-term survival in the same population was evaluated. METHODS: This was a prospective (NCT04825080; CARAS-Carotid Asymptomatic Stenosis Study) observational cohort study including patients with ACAS>60% (NASCET criteria) started in 2019 and ended in 2025. Patients were not considered for carotid revascularization because of high surgical risk or the absence of plaque vulnerability features. BMT was defined as regular intake of antiplatelet therapy and statins, blood pressure control, and cessation/absence of smoking. Follow-up included annual clinical visits and six-month telephone interviews. The primary endpoint was overall survival, stratified by age (<80 years,81-85 years,>85 years). Secondary analyses aimed to identify independent predictors of mortality and to develop a mortality risk score. RESULTS: A total of 307 patients were included (mean age 80±7 years;55% male). Contralateral carotid stenosis>60% was present in 61 patients (20%). At the end of follow-up, 86% of patients were under BMT. The overall TIA/stroke rate was 1.3% / year, with higher risk for contralateral stenosis (1.9%) and plaque progression (1.8%). The overall 5-year survival rate was 80±2%, with age-related differences: 90±2% in patients <80 years,75±4% in those aged 81-85 years and 67±6% in patients >85 years(p<.001). Multivariable Cox regression identified diabetes mellitus(DM)(HR 2.2,95%CI 1.5-3.3;p<.001), chronic kidney disease(CKD)(HR 2.2,95%CI 1.3-3.8;p<.001), coronary artery disease(CAD)(HR 2.0,95%CI 1.3-3.0;p<.001), age 81-85 years(HR 2.5,95%CI 1.5-4.1;p<.001), and age >85 years(HR 3.5,95% CI 2.1-5.8;p<.001) as independent predictors of mortality. Based on these variables, a mortality score was developed: 1 point each for DM, CKD, CAD, and age 81-85 years, and 2 points for age >85 years. ROC curve analysis identified a score >3 as highly specific for patients at high risk (area under the curve: 75%). Patients with a score >3 had significantly lower 5-year survival (52%) compared with those with a score ≤3(87%;p<.001). CONCLUSIONS: In patients with ACAS under BMT, 5-year survival is high and it is driven more by comorbid clinical conditions than by advanced age alone. These findings may help refine patient selection and risk stratification when considering carotid revascularization.