Safety and efficacy of percutaneous patent foramen ovale closure compared with anti-thrombotic therapy for people with cryptogenic stroke: a systematic review and meta-analysis.

BACKGROUND

Stroke is a leading cause of death and disability. Patent foramen ovale (PFO) is more common in cryptogenic stroke, but the benefit of closure over antithrombotic therapy remains debated. We updated randomized evidence comparing PFO closure with antithrombotic therapy.

METHODS

MEDLINE, Embase, and Cochrane Central were searched through September 2025. Primary outcomes were stroke, transient ischemic attack (TIA), and a composite of stroke, TIA, death, or systemic embolism. Serious adverse events and atrial fibrillation were assessed.

RESULTS

Six trials (n = 3,560; closure 1,889; therapy 1,671) were included. Composite events occurred in 84 (4.4%) vs 152 (9.1%). Closure reduced the composite endpoint (HR 0.46, 95% CI 0.28-0.75; p = 0.002) and recurrent stroke (37 [2.0%] vs 77 [4.6%]; HR 0.27, 95% CI 0.12-0.62; p = 0.002). Benefit was greatest in men, age <45 years, and those with large shunts. Serious adverse events and mortality were similar, but atrial fibrillation increased (HR 4.46, 95% CI 2.00-9.92; p < 0.001).

CONCLUSION

In selected patients, PFO closure lowers recurrent stroke and composite events versus antithrombotic therapy, at the cost of higher atrial fibrillation.

PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD420251167260.