Antithrombotic treatment for migraine in patients with patent foramen ovale: multicentre, randomised, active controlled, open label trial.

Summary

This investigator-initiated trial randomized 984 adults with echocardiographically confirmed patent foramen ovale and frequent migraine to aspirin, clopidogrel, rivaroxaban, or metoprolol for 12 weeks. Responder rates were 61.7% for aspirin, 66.8% for clopidogrel, 78.4% for rivaroxaban, and 61.8% for metoprolol; all antithrombotic agents were non-inferior to metoprolol, and rivaroxaban was superior. No major bleeding events occurred during the treatment period.

Key Findings

• Among 984 participants in the full analysis set, responder rates were 61.7% with aspirin, 66.8% with clopidogrel, 78.4% with rivaroxaban, and 61.8% with metoprolol.
• Aspirin, clopidogrel, and rivaroxaban were all non-inferior to metoprolol for achieving at least a 50% reduction in monthly migraine days or attacks.
• Rivaroxaban was superior to metoprolol, with an absolute responder-rate difference of 16.2% and no major bleeding events.

Clinical Implications

In adults with patent foramen ovale and frequent migraine, antithrombotic therapy may be considered as an alternative preventive strategy when clinically appropriate. The findings do not justify routine anticoagulation solely for migraine because bleeding risk, PFO anatomy, stroke history, and individual cardiovascular indications must be incorporated into shared decision-making.

Limitations

• The open-label treatment design may have introduced performance and expectancy bias despite blinded outcome assessment.
• The 12-week treatment period was short for evaluating long-term thromboembolic prevention, bleeding risk, and sustained migraine control.

Future Directions

Future trials should compare antithrombotic strategies with contemporary migraine preventives over longer periods, stratify participants by PFO shunt characteristics and embolic risk, and assess whether selected subgroups derive sufficient benefit to justify anticoagulation. Comparative studies with PFO closure would also be informative.