Progression of asymptomatic carotid stenosis despite optimal medical therapy

Abstract

Despite level 1 evidence in support of carotid endarterectomy vs medical therapy in selected asymptomatic patients, an alternative posture is that optimal medical therapy (OMT) has not been adequately studied and that such OMT has reduced stroke risk in asymptomatic patients to levels wherein carotid endarterectomy is no longer justified. The goal of this study was to determine the natural history of patients with asymptomatic moderate (50%-69%) carotid artery stenosis (AMCAS) in a contemporary cohort as a function of their associated medical therapy. Patients with AMCAS determined by duplex ultrasound (DUS) from 2005-2006 were identified in our hospital database. Patients were included in the cohort if they had at least one additional DUS during the 6-year follow-up interval. Patient characteristics including medication history and lipid levels were collected. Patients were considered to have OMT if they were on aspirin and a statin with a low-density lipoprotein level that was always <100 mg/dL. Study end points included progression of carotid disease by DUS to severe stenosis (70%-100%), development of ipsilateral neurologic symptoms (INS) such as stroke or transient ischemic attack, and death. There were 900 carotid arteries in 794 patients in the study cohort. The average age was 72.5 years, 77.2% had hypertension, 59.6% had coronary artery disease, and 87.1% were on a statin throughout the study. The low-density lipoprotein cholesterol level was always normal (<100 mg/dL) in 37.8% and accordingly, 241 (30.3%) had OMT as defined above. The 5-year actuarial survival was 81.9% ± 1.3% with no advantage seen with OMT. Multivariate analysis of survival showed statins were protective (hazard ratio [HR], 0.50; confidence interval [CI], 0.34-0.73; P = .0004). The 5-year freedom from plaque progression was 61.2% ± 2.1% with no benefit from OMT vs the control group. Multivariate predictors of plaque progression were chronic kidney disease (HR, 2.1; CI, 1.2-3.7; P = .009), aspirin use (HR, 1.9; CI, 1.2-3.0; P = .01), and the use of calcium channel blockers (HR, 1.4; CI, 1.1-1.8; P = .007). There were 90 (11.3%) patients who developed INS during follow-up (58% of these were strokes), and the 5-year freedom from INS was 88.4% ± 1.5%. Multivariate predictors of INS were diabetes (HR, 2.3; CI, 1.5-3.6; P = .0002) and warfarin use (HR, 1.9; CI, 1.2-2.9; P = .009); while statin use (HR, 0.37; CI, 0.22-0.65; P = .0005) was protective against symptom development. At the 5-year of follow-up, OMT failed to prevent carotid disease progression or development of ipsilateral symptoms in 45% of patients with AMCAS.