Background and Purpose-The risk of stroke recurrence in patients with Embolic Stroke of Undetermined Source (ESUS)is high, and the optimal antithrombotic strategy for secondary prevention is unclear. We investigated whether congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA; CHADS 2 ) and CHA 2 DS 2 -VASc scores can stratify the long-term risk of ischemic stroke/TIA recurrence and death in ESUS. Methods-We pooled data sets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox regression analyses were performed to investigate if prestroke CHADS 2 and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category (CHA 2 DS 2 -VASc) scores were independently associated with the risk of ischemic stroke/TIA recurrence or death. The Kaplan-Meier product limit method was used to estimate the cumulative probability of ischemic stroke/TIA recurrence and death in different strata of the CHADS 2 and CHA 2 DS 2 -VASc scores. Results-One hundred fifty-nine (5.6% per year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in 1095 patients (median age, 68 years) followed-up for a median of 31 months. Compared with CHADS 2 score 0, patients with CHADS 2 score 1 and CHADS 2 score >1 had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40, respectively) and death (HR, 3.58; 95% CI, and HR, 5.45; 95% CI, respectively). Compared with low-risk CHA 2 DS 2 -VASc score, patients with high-risk CHA 2 DS 2 -VASc score had higher risk of ischemic stroke/TIA recurrence (HR, 3.35; 95% CI,) and death (HR, 13.0; 95% CI, Ntaios et al Risk Stratification in ESUS 2279T he term Embolic Stroke of Undetermined Source (ESUS) has been introduced by the Cryptogenic Stroke/ESUS International Working Group to include patients with ischemic stroke for whom the source of embolism remains unidentified despite recommended investigation; potential embolic sources include covert atrial fibrillation (AF), the mitral and aortic valves, the left cardiac chambers, the proximal cerebral arteries of the aortic arch, and the venous system via paradoxical embolism.1,2 The risk of stroke recurrence is higher in ESUS patients than in patients with noncardioembolic strokes, which could be a sign that current antithrombotic strategy of treating ESUS patients with antiplatelet agents may be suboptimal. 3,4 In this context, 3 randomized trials are currently under way to assess whether antiplatelet or oral anticoagulation is the optimal treatment in ESUS patients. 5-7The congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA) (CHADS 2 ) and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex catego...

Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.

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