In individuals who had embolic stroke of unknown source (ESUS) and carotid atherosclerosis, treatment with aspirin was safer than with rivaroxaban (Xarelto; Janssen Pharmaceuticals, Raritan, NJ) and as effective for prevention of secondary stroke. An exploratory subgroup analysis of outcomes for participants in the NAVIGATE-ESUS trial (NCT02313909). Of those who participated in the trial, 40% had carotid artherosclerosis (defined as carotid stenosis of 20%-49% or presence of carotid stenosis (n = 490) and 11% had carotid stenosis. For those with carotid stenosis, the hazard ratio (HR) for secondary stroke when treated with aspirin was 0.85 (95% CI, 0.39-1.87; P = .78 for interaction of treatment effect with group without carotid stenosis). For those with carotid plaque, the HR was 1.20 (95% CI, 0.86–1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2).
For participants with carotid plaque, major bleeding was more frequent in those treated with rivaroxaban compared with aspirin (HR = 3.75; 95% CI, 1.63–8.65). Although participants with carotid stenosis had a similar rate of secondary ischemic stroke compared with those without (HR = 1.11; 95% CI, 0.73–1.69), there was a strong trend of higher rate of secondary ischemic stroke recurrence in people with carotid plaque vs those without (HR, 1.23; 95% CI, 0.99–1.54).
Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS.