PRIMA: PFO Closure Fails to Reduce Number of Migraine Days at 1 Year

In patients with refractory migraine headaches with aura, patent foramen ovale (PFO) closure does not reduce the total number of migraine days within 1 year, but does lower the frequency of migraine with aura, according to a late-breaking trial presented at TCT 2014.

For the PRIMA trial, David Hildick-Smith, MD, of Sussex Cardiac Center, Brighton, United Kingdom, and colleagues enrolled 107 patients diagnosed as having migraine with aura that does not respond to preventative medical treatment (>3 migraine attacks or ≥5 migraine days per month). Patients were randomly assigned to receive PFO closure with the Amplatzer device (St. Jude Medical; n=53) or medical therapy (n=54) at 20 sites in Canada, Germany, Switzerland and the United Kingdom. All patients received 6 months of aspirin and 3 months of clopidogrel.

At 1-year follow-up, PFO closure did not significantly reduce the primary endpoint of migraine days (see Figure on page 10). However, device implantation was associated with a reduction in migraine with aura days (P=.01) and the number of attacks (P<.01).

PFO closure was also linked with a greater responder rate (≥50% reduction in number of migraine days) compared with medical therapy (37.5% vs. 14.6%; P=.02). More closure patients reported freedom from migraine (10% vs. 0) and freedom from migraine with aura (40% vs. 10%) than those treated with medical therapy (P<.05 for both).

In the closure group there was one major vascular complication with bleeding and one episode of atrial fibrillation requiring direct-current cardioversion. No major adverse events were reported in the medical therapy group.

Hildick-Smith noted several study limitations: high screen-to-recruitment ratio, long recruitment phase, unblended study nature, high post-randomization dropout, high failure of PFO closure patients to undergo treatment and early termination.

Looking to PREMIUM 

“Interventional studies in migraine with aura patients are difficult to do,” he said. “Only 40% of patients in PRIMA had right-to-left shunt.” Yet, there is an “unequivocal relationship” between PFO, closure, migraine and migraine with aura, Hildick-Smith continued.

“Real and tangible benefit accrues [in] some migraine patients after PFO closure,” he concluded, adding that results of the upcoming PREMIUM trial, comparing PFO closure with a sham procedure in the same patient group, should give more insight.

In both the panel and online discussions, many panelists and audience members cited the need for sham control and a larger patient population. Although panel moderator Ajay J. Kirtane, MD, SM, of Columbia University Medical Center, New York, N.Y., called PRIMA a “formidable effort,” digital moderator Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital, Boston, Mass., said that the current study design “greatly limits the broad applicability of the results.”

Average patient age in PRIMA was 44 years, and more than 80% were women. Most patients (98%) were unresponsive to at least two preventative migraine medications and reported aura with more than half of their migraine events.

 

Disclosures: 

  • Bhatt reports relationships with multiple device and pharmaceutical companies.
  • Hildick-Smith reports receiving grant/research support and consultant fees/honoraria from St. Jude Medical.
  • Kirtane reports relationships with multiple device companies.
  • The PRIMA trial was sponsored by St. Jude Medical.

 

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