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

ABSTRACT

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.

KEYWORDS:

• Cryptogenic Stroke
• PFO Closure
• embolic stroke of undetermined source
• novel oral anticoagulants
• antiplatelets

Article Highlights

• PFO Closure reduces the risk of recurrent stroke in young patients with cryptogenic stroke

• Methodological and treatment-related differences may help to explain discrepancies in the results between older and newer PFO closure randomized control trials

• Identification of ‘high-risk’ PFO is critical in choosing patients with cryptogenic stroke that may benefit from PFO closure, while continuation of antiplatelet therapy is necessary after device implantation

• Use of novel oral anticoagulants did not confer recurrent stroke reduction benefit in patients with cryptogenic stroke in two large randomized control trials

• Differences in the patient characteristics between PFO closure and novel oral anticoagulants trials highlight the diversity of cryptogenic stroke.

Acknowledgments

I would like to thank both Ms. Natasha Kohli and Dr. Anita Asgar for their time and patience.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.