Patent foramen ovale closure versus medical therapy for prevention of recurrent ischemic events in patients with cryptogenic stroke or transient ischemic attack and documented patent foramen ovale: a systematic review and network meta-analysis of randomized controlled trials and observational studies.

BACKGROUND

This network meta-analysis (NMA) aimed to compare the efficacy and safety of patent foramen ovale (PFO) closure and medical therapy categories, including antiplatelet therapy, anticoagulation, and mixed medical therapy.

METHODS

We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science from inception to June 22, 2026. Eligible randomized controlled trials and observational studies comparing PFO closure with medical therapy in adult patients with cryptogenic ischemic stroke or transient ischemic attack and confirmed PFO were included.

RESULTS

Eighteen studies involving 7,135 participants, including six randomized controlled trials and 12 observational studies, were included. Four intervention nodes were analyzed: PFO closure, antiplatelet therapy, anticoagulation, and mixed medical therapy. For recurrent cerebrovascular ischemic events, PFO closure was associated with a lower risk than antiplatelet therapy (RR 0.22, 95% CI 0.12-0.41), anticoagulation (RR 0.40, 95% CI 0.19-0.82), and mixed medical therapy (RR 0.51, 95% CI 0.33-0.77). For bleeding events, PFO closure was associated with a significantly lower risk than anticoagulation (RR 0.16, 95% CI 0.06-0.42), while the comparisons with antiplatelet therapy (RR 0.49, 95% CI 0.20-1.23) and mixed medical therapy (RR 0.91, 95% CI 0.46-1.79) did not reach statistical significance. Model-fit assessment showed similar DIC values between the consistency and unrelated mean-effects models.

CONCLUSIONS

PFO closure showed the most favorable efficacy profile for preventing recurrent cerebrovascular ischemic events and was associated with a significantly lower bleeding risk than anticoagulation. However, safety findings for comparisons with antiplatelet therapy and mixed medical therapy should be interpreted cautiously because bleeding events were sparse and confidence intervals were wide.

SYSTEMATIC REVIEW REGISTRATION: CRD420251148908.