Research Summary

Rivaroxaban Improves Migraine Response in Adults With Patent Foramen Ovale

Edited by:
Ashton L. Stahl

Key Highlights

  • Aspirin, clopidogrel, and rivaroxaban were noninferior to metoprolol for the primary responder outcome.
  • Rivaroxaban produced a higher responder rate than metoprolol: 78.4% versus 61.8%.
  • No major bleeding events occurred during the 12-week intervention.
  • The authors characterized the results as hypothesis-generating and called for confirmation in larger, rigorously blinded trials.

Three antithrombotic agents were noninferior to metoprolol for migraine response among adults with patent foramen ovale (PFO). Rivaroxaban also demonstrated superiority over the active comparator in the randomized COMPETE trial published in The BMJ.

The investigator-initiated COMPETE trial enrolled 1,000 adults aged 18 to 64 years from 39 secondary and tertiary care centers in mainland China. Eligible participants had experienced migraine for more than 1 year, reported at least 4 migraine days per month, and had echocardiographically confirmed PFO.

After a 12-week screening period, participants were randomly assigned in equal proportions to aspirin 300 mg once daily, clopidogrel 75 mg once daily, rivaroxaban 20 mg once daily, or metoprolol 25 mg twice daily for 12 weeks. The trial used an open-label design with blinded outcome assessment. The full analysis set included 984 participants, of whom 75.1% were women; the median age was 38.5 years. The primary efficacy analysis used complete cases within the full analysis set, excluding 40 participants without primary endpoint data.

The primary outcome was the proportion of participants achieving at least a 50% reduction in monthly migraine days or attacks from baseline to weeks 9 through 12. Safety outcomes included bleeding and other adverse events.

Study Findings

Primary endpoint responder rates were 61.7% with aspirin, 66.8% with clopidogrel, 78.4% with rivaroxaban, and 61.8% with metoprolol. All 3 antithrombotic agents met the prespecified criterion for noninferiority to metoprolol.

Rivaroxaban was the only treatment that demonstrated superiority over metoprolol, with an absolute difference in responder rate of 16.2% (98.33% CI, 6.0%-26.4%; P< .001). Rivaroxaban also had higher responder rates than aspirin and clopidogrel, with respective differences of 16.6% and 11.6%.

Complete migraine cessation occurred in 32.6% of participants receiving rivaroxaban, compared with 21.7% receiving aspirin, 20.4% receiving clopidogrel, and 20.2% receiving metoprolol. Rivaroxaban was also associated with greater reductions in migraine days and attacks and greater improvements in migraine-specific quality-of-life scores than metoprolol.

No major bleeding events occurred. Any bleeding was reported in 10.1% of the aspirin group, 8.2% of the clopidogrel group, and 11.4% of the rivaroxaban group, compared with none in the metoprolol group.

Clinical Implications

According to the study authors, the findings provide early directional evidence that antithrombotic pathways may influence migraine burden in patients with PFO and suggest that a possible microembolic mechanism contributes to migraine in this population. They cautioned that rivaroxaban’s numerical advantages should not be interpreted as evidence for replacing first-line preventive treatments.

The authors identified the open-label design, self-reported headache diaries, relatively low metoprolol dose, 3-month treatment duration, and limited generalizability beyond the predominantly young, female, East Asian population as limitations. They characterized the trial as hypothesis-generating and stated that the observations require confirmation in larger, rigorously blinded studies.

Expert Commentary

“Rivaroxaban also showed superiority over metoprolol, resulting in a higher responder rate without an increase in major bleeding events,” the researchers concluded.

Reference

Li Z, Wang C, Tang Y, et al. Antithrombotic treatment for migraine in patients with patent foramen ovale: multicentre, randomised, active controlled, open label trial. BMJ. 2026;394:e100103. doi:10.1136/bmj-2026-100103