Medical Device Daily Associate
PARIS – The idea that fixing a congenital defect of the heart can help to alleviate migraine headaches received another shot in the arm with preliminary release of data from the Migraine Intervention with STARflex Technology (MIST) trial here at the cavernous Palais de Congr s.
The condition, known as a patent foramen ovale (PFO), is an incomplete closure of the atrial membrane of the heart and has been implicated, although not conclusively proven, to cause various neurological disorders such as stroke or migraine headaches. Awareness of its potential role in these disorders has dramatically increased in recent years.
The trial uses NMT Medical’s (Boston) STARflex septal repair technology to close the PFO in a minimally invasive procedure. The PFO closure procedure using STARflex takes about 30 minutes to perform in a cardiac catheterization lab. Patients can return to normal activity soon after the procedure.
The company initiated enrollment in the study in January (Medical Device Daily, Jan. 10, 2005). It said at EuroPCR that the trial is slated for complete enrollment by the end of June – well ahead of schedule.
MIST is the first prospective, randomized, controlled study to evaluate the potential relationship between PFO, a common structural heart defect, and certain migraine headaches. It is believed that a PFO allows venous blood, unfiltered by the lungs, to shunt, or flow, into the arterial circulation of the brain. This unfiltered venous blood may contain elements that possibly trigger migraine headaches or other brain attacks in some patients.
Data on the incidence of PFO observed in the multi-center MIST study was presented by Peter Wilmshurst, MD, consultant cardiologist at the Royal Shrewsbury Hospital (Shrewsbury, UK), at a late-breaking trials session.
In a press conference after his presentation, Wilmshurst, who also is co-primary investigator for the trial, said, “In our evaluation of 370 migraine patients, we found that 50% of them had a PFO, which allows a right to left shunt, or flow, of venous blood into the arterial circulation. This important finding is consistent with earlier observational data and is twice what one would expect to find in the general population.”
In addition to PFOs, he said researchers found other shunts, predominately pulmonary, “in another 10% of the migraine patients studied, which again is greater than what one would expect.”
What is remarkable, he said, is that more than 40% of the migraine patients studied had a large shunt; “this is six times greater than what would be expected in the general population. By far, the PFO was the most prevalent large shunt we saw in the migraine patients, accounting for over 85% of all large shunts detected.”
Interestingly, he said, this unusually high incidence was found in a group of people who have frequent migraine attacks with aura, but are otherwise healthy and have no symptoms to indicate a heart defect.
Previous studies have reported finding PFOs in 27% of the general patient population with only 7% of them being large.
Wilmhurst, an avid diver, first became familiar with PFOs when he studied their association with decompression illness, also known as “the bends,” back in 1986.
His work on PFO in divers led to observing a high rate of migraine in those with PFO and the observation that when PFOs were closed, migraine was improved or cured.
Andrew Dowson, MD, director of the King’s Headache Service, Kings College Hospital (London), the other co-lead investigator, said during the press conference that he found the initial data from MIST to be intriguing.
“We are not certain what causes migraine headaches,” he said. “If, however, shunts like the PFO allow venous blood to enter the cerebral circulation, unfiltered and unmanaged by the lungs, perhaps that venous blood contains materials that trigger migraines in some patients.”
The next question the MIST study is designed to answer is whether closing the PFO with the STARflex implant technology reduces or eliminates migraine headaches.
“We should be able to provide an answer to that question by the end of this year or early next year,” Dowson said.
To date, NMT Medical said, more than 15,000 PFOs have been closed globally with its implant technology, but migraine is a potentially lucrative new application for the technology originally designed for the treatment of recurrent stroke and transient ischemic attack.
In a conference call that coincided with the initiation of enrollment in January, NMT said that the new indication could have a more immediate impact on the company’s growth than that of its initial stroke focus.
“The initiation of our MIST trial is a landmark event for NMT as we expand our PFO closure focus beyond stroke to other brain attacks,” said President and CEO John Ahern. “We believe that PFO closure for migraine represents a substantial and more immediate revenue growth opportunity for NMT as compared to stroke.”
He also said that he believes the initial target patient population for PFO closure with the company’s technology would be 5% of all migraine sufferers, a number that he based on statistics from the World Health Organization (Geneva, Switzerland) and the American Council for Headache Evaluation (Mt. Royal, New Jersey), which indicates the prevalence of migraines in the U.S., Europe and Japan is about 10% of the general population.
Ahern also noted that published medical research indicates that about 20% of migraine sufferers have migraine with aura, often referred to as the classic migraine, and that up to 50% of those suffering from migraine with aura are unresponsive to current medications, another requirement for enrollment in the study.
The target market for the devices, which cost about $5,000, is about 1.5 million patients in the U.S., with another 2.5 million via the international market
The MIST study’s patient recruitment process was supported by the Migraine Action Association (MAA), a migraine headache advocacy group representing more than 14,000 members in the UK.