NOMAS: Just a 2% Overlap for PFO and Migraine; St Jude Shuts Down ESCAPE Trial

Shelley Wood

October 09, 2008

October 9, 2008 (Miami, FL) — Delivering another blow to the theory that patent foramen ovale (PFO) can cause migraine headaches, researchers in Florida are reporting that in a large, multiethnic cohort the prevalence of either condition is about 15%, but the two are only rarely present in the same person [1]. Using data from the Northern Manhattan Study (NOMAS), Dr Tatjana Rundek (University of Miami, FL) and colleagues found that only 2% of subjects had both PFO and self-reported migraine.

Their results are published in the September 30, 2008 issue of Circulation.

In other news, heartwire has learned that another company has quietly pulled the plug on its trial investigating PFO closure for migraine.

Discussing the results with heartwire , Rundek pointed out that earlier studies have tended to first identify a population of patients with PFO and then go looking for migraine prevalence or to first identify a population of patients with migraine and then test them for PFO. Their study specifically started with a population in whom neither the PFO rates nor presence/absence of migraine was known at baseline.

In NOMAS, 1101 stroke-free subjects, mean age 69, were asked about their history of migraine, then screened for PFO using transthoracic echocardiography. In all, 16% of the population reported a history of migraine (13% migraine with aura), and 15% were found to have PFO. But strikingly, prevalence of PFO was no different in subjects with or without migraine (14.6% vs 15%), nor was PFO associated with increased prevalence of migraine after adjustment for possible confounders, including diabetes, hypertension, smoking, or dyslipidemia.

"The main message here is that both conditions are prevalent, but having both is not that prevalent," Rundek told heartwire . "In this population, which is a little bit older than other case-controlled studies, we're pretty confident that this association does not exist. However, we cannot make this conclusion for a younger population."

But the causative-link hypothesis seems to be crumbling, along with hopes that PFO closure might help migraineurs. As previously reported by heartwire , the MIST I trial found no benefit of PFO closure using NMT Medical's Starflex device, compared with a sham procedure, in terms of migraine cure or reduction in migraine days. AGA Medical has two studies of PFO closure for migraine using its Amplatzer device still enrolling patients (the US PREMIUM trial and the international PRIMA trial), but a third company, St Jude Medical, has stopped enrollment in its ESCAPE trial, which was testing its Premere device as a treatment for migraine. A company spokesperson confirmed that just 56 patients out of a planned 492 subjects had been enrolled since 2006. "The company has determined that it is not reasonable to continue the study," she said.

Rundek said she is disappointed, if unsurprised, to hear of ESCAPE's halt. "My opinion all along was, let's finish the studies and get some answers, as long as there are no concerns about safety."

But she also commented that the theory had always, to her, seemed too good to be true. "Migraine either with or without aura is a very complicated disorder in terms of the pathophysiology, and the mechanisms are still not clearly known to the full extent. It's hard to believe that having a PFO would be completely linked to such a complex mechanism of migraine and that by closing PFO we would completely eradicate migraine," she said. Earlier studies reporting a link between PFO and migraine "speak more to maybe some underlying genetic mechanism or some specific polymorphism that actually predisposes people to have both conditions than actually having the conditions linked through a certain mechanism," she speculated.

Don't Go Hunting forPfos in Migraineurs

In an editorial accompanying the NOMAS study, Dr Tobias Kurth (Brigham and Women's Hospital, Boston, MA) et al point to the scant evidence linking migraine with PFO in case-control studies; linking people with migraine with aura, who also have PFO, to an increased risk of stroke; or linking PFO closure to effective migraine treatment [2].

"Thus, detection of PFO or PFO closure should not be recommended to patients who have only migraine," they conclude. "It is, however, plausible that PFO may affect specific subgroups of patients with migraine, and future studies identifying and targeting such subgroups are warranted."

Indeed, an observation made by both the editorialists and the NOMAS study authors is that these particular results are confined to an older group of patients, in whom prevalence of migraine tends to be lower than in younger patients.

Also commenting on the NOMAS findings for heartwire , Dr Randy Evans (Baylor College of Medicine, Houston, TX), had similar views, saying that the link between migraine, stroke, and PFO "is becoming more and more tenuous."

"Despite several positive observational studies, the controversial MIST trial showed no improvement in migraine frequency with PFO closure," he noted. "And now, despite case-control studies showing an association between migraine with aura and PFO, the population-based NOMAS study shows no association."

Population-based studies generally have the least bias, Evans pointed out, although in the case of NOMAS, there may have been "ascertainment bias," since the authors relied on participant self-reporting with regard to their migraine history. The older age of the patients might also have played a role, leading to "recall bias," he added.

"For now, the evidence does not support closing PFOs in migraineurs with aura," Evans said. "However, several further studies are ongoing with different closure devices; perhaps the results will be positive and lead to even more controversy."

  1. Rundek T, Elkind MSV, Di Tullio MR, et al. Patent foramen ovale and migraine. A cross-sectional study from the Northern Manhattan Study (NOMAS). Circulation 2008; 118:1419-1424. Abstract

  2. Kurth T, Tzourio C, Bousser MG. Migraine: A matter of the heart? Circulation 2008; 118:1405-1407. Abstract

The complete contents of Heartwire , a professional news service of WebMD, can be found at, a Web site for cardiovascular healthcare professionals.



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