Abstract

Introduction: Trials are underway to evaluate the prophylactic use of novel oral anticoagulants (NOAC) in patients with embolic strokes of undetermined source (ESUS). It is uncertain whether the bleeding risks associated with prophylactic NOAC use will outweigh any stroke prevention benefit in ESUS patients who lack underlying atrial fibrillation (AF). Methods: We determined the proportion of patients in the CRYSTAL AF study who met ESUS trial criteria and had AF (≥2 minutes) detected within 3 years via an insertable cardiac monitor (ICM). Cryptogenic stroke patients ≥50 years old with a modified Rankin score ≤3 and no evidence of lacunar infarcts after an extensive stroke work up were included. Age ≥60 years and CHA 2 DS 2 VASc score ≥3 were required for patients whose index stroke occurred 3-6 months before randomization. We also compared AF detection rates between the ICM and standard monitoring arms using Kaplan-Meier estimates and computed the percentage of patients with AF detected within the initial 30 days of ICM monitoring. Results: Among the 441 patients enrolled in CRYSTAL AF, 246 (55.8%) met inclusion criteria for the ongoing ESUS trials. AF detection rates at 3 years reached 38.5% in the ICM arm vs. 2.7% in the control arm (HR 12.1 [3.7-39.3], p<0.0001, Figure). In contrast, AF detection rates at 30 days were only 6.7% and 0.8% in the ICM and control arm, respectively. Conclusions: Among the subset of CRYSTAL AF patients who met the ESUS trial criteria, >60% did not have AF detected via ICMs within 3 years of their index stroke event. Prophylactic NOAC use in the absence of AF may therefore increase bleeding risks without providing protection against AF-related stroke in the majority of ESUS patients. Furthermore, ICMs were superior to standard monitoring for AF detection in this ESUS population. Monitoring continuously for only the initial 30 days would have failed to identify AF in >80% of patients ultimately found to have AF via an ICM.

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