Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source

<jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> We aimed to assess the prevalence and degree of overlap of potential embolic sources ( <jats:styled-content style="fixed-case">PES</jats:styled-content> ) in patients with embolic stroke of undetermined source ( <jats:styled-content style="fixed-case">ESUS</jats:styled-content> ). </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> In a pooled data set derived from 3 prospective stroke registries, patients were categorized in ≥1 groups according to the <jats:styled-content style="fixed-case">PES</jats:styled-content> that was/were identified. We categorized <jats:styled-content style="fixed-case">PES</jats:styled-content> as follows: atrial cardiopathy, atrial fibrillation diagnosed during follow‐up, arterial disease, left ventricular disease, cardiac valvular disease, patent foramen ovale, and cancer. In 800 patients with ESUS (43.1% women; median age, 67.0 years), 3 most prevalent <jats:styled-content style="fixed-case">PES</jats:styled-content> were left ventricular disease, arterial disease, and atrial cardiopathy, which were present in 54.4%, 48.5%, and 45.0% of patients, respectively. Most patients (65.5%) had >1 <jats:styled-content style="fixed-case">PES</jats:styled-content> , whereas only 29.7% and 4.8% of patients had a single or no <jats:styled-content style="fixed-case">PES</jats:styled-content> , respectively. In 31.1% of patients, there were ≥3 <jats:styled-content style="fixed-case">PES</jats:styled-content> present. On average, each patient had 2 <jats:styled-content style="fixed-case">PES</jats:styled-content> (median, 2). During a median follow‐up of 3.7 years, stroke recurrence occurred in 101 (12.6%) of patients (23.3 recurrences per 100 patient‐years). In multivariate analysis, the risk of stroke recurrence was higher in the atrial fibrillation group compared with other <jats:styled-content style="fixed-case">PES</jats:styled-content> , but not statistically different between patients with 0 to 1, 2, or ≥3 <jats:styled-content style="fixed-case">PES</jats:styled-content> . </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> There is major overlap of <jats:styled-content style="fixed-case">PES</jats:styled-content> in patients with <jats:styled-content style="fixed-case">ESUS</jats:styled-content> . This may possibly explain the negative results of the recent large randomized controlled trials of secondary prevention in patients with ESUS and offer a rationale for a randomized controlled trial of combination of anticoagulation and aspirin for the prevention of stroke recurrence in patients with <jats:styled-content style="fixed-case">ESUS</jats:styled-content> . </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Clinical Trial Registration</jats:title> <jats:p xml:lang="en"> <jats:styled-content style="fixed-case">URL</jats:styled-content> : <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifier: <jats:styled-content style="fixed-case">NCT</jats:styled-content> 02766205. </jats:p> </jats:sec>