Examining the evidence for PFO closure and novel oral anticoagulants for treatment of cryptogenic stroke.

Introduction: There has been considerable study assessing the treatment of cryptogenic stroke (CS) recently. This review examines the role of patent foramen ovale (PFO) closure in CS, while also discussing the evidence for alternative medical therapies in disease treatment.Areas covered: PFO closure for treatment of CS has been assessed in 6 randomized controlled trials (RCTs). This review summarizes the background, results and limitations of these trials. Methodological and treatment-related differences in RCTs provide potential explanations for the discordance in outcomes observed between older (CLOSURE, PC, RESPECT-Early) and newer PFO closure trials (RESPECT-Late, CLOSE, REDUCE, DEFENSE-PFO). With regards to medical therapy for CS, two RCTs (NAVIGATE ESUS and RE-SPECT ESUS) did not show any benefit in recurrent stroke prevention with the use of novel oral anticoagulants (NOAC) compared with aspirin. Marked differences in baseline characteristics and rates of recurrent stroke between PFO closure and NOAC trials underlie the heterogeneous nature of CS.Expert commentary: In young patients with CS, PFO closure reduces the risk of recurrent stroke, with newer RCTs emphasizing the importance of identifying those with 'high-risk' PFO and the need for continued antiplatelet therapy. Additionally, treatment for CS should not be uniform but directed at disease-specific pathologies.