The results are in on the MIST

Migraine sufferers who want to know more about patent foramen ovale (PFO) and a possible connection to Migraine should be interested in the results of the MIST (Migraine Intervention with STARFlex® Technology) study. MIST was the British double-blind study designed to evaluate the effect of PFO (patent foramen ovale) closure on Migraine. (See: PFO and Migraine -: "Hole in the Heart and Migraine?.)

Doctors Peter Wilmshurst and Andrew Dowson, co-primary investigators of MIST, jointly presented the results on March 13, 2006, at the American College of Cardiology's 55th Annual Scientific, Late-Breaking Clinical Trials Sessions. Dr. Wilmshurst is Consultant Cardiologist at Royal Shrewsbury Hospital, Shrewsbury. Dr. Dowson is Director of the King's Headache Service, Kings College Hospital, London.

MIST, which was conducted in the United Kingdom, is the first prospective, randomized, double-blinded study to evaluate the effect of PFO (patent foramen ovale) closure on Migraine headaches. NMT 's proprietary PFO closure technology, STARFlex®, was exclusively used in the study. A PFO is a common heart defect that is a risk factor for Migraine headaches in some patients. The PFO allows venous blood, unfiltered and unmanaged by the lungs, to enter the arterial blood circulation. The unfiltered venous blood may contain elements that can trigger Migraines in some patients.

The study, screened 432 Migraine with aura patients for a PFO and enrolled 147 patients into the study. A significant finding in the MIST study is that over 60% of those screened had a right to left shunt, a heart defect, which allows blood to cross from the right to left chambers of the heart, bypassing the lungs. Of those patients, almost 40% had a moderate or large PFO, six times greater than the general population.

Dr. Wilmshurst said,

"With no prior randomized, double blind study to draw from, MIST was designed and primary endpoints were selected based upon a review and analysis of several previously reported device observational and Migraine drug studies. Consistent with what was reported in the observational studies, we selected a challenging primary endpoint of 40% elimination in Migraine headache at six months in the treatment group. Preliminary analysis of MIST data did not satisfy that endpoint, however, we are seeing a significant treatment effect and promising trend to support PFO closure with STARFlex® as a treatment option for certain types of Migraine."

The MIST results indicated an approximate 37% reduction in Migraine burden (number of headaches multiplied by the length, in hours of headache) in those patients who received a STARFlex® implant and a 17% reduction in those who received the sham procedure and no implant (essentially, a placebo). This represents a statistically significant treatment effect. It also was reported that this variance appears to increase over time.

Dr. Dowson commented,

"For the first time we can see trends in a prospective study to suggest that PFO closure may be an effective way to treat certain types of Migraine. A reduction in headache burden for a patient with severe Migraine may allow that individual to gain more control and lead a more fulfilling and productive life. The key now will be establishing the criteria that will help to determine which patients should be referred to the interventional cardiologist for further treatment."

Dr. Wilmshurst added,

"This study significantly increases our understanding of those patients who might benefit from cardiac intervention to treat these debilitating headaches. The results, arising from an unprecedented collaboration between cardiac and headache doctors, are a precursor to what we believe could be an exciting development in Migraine treatment."

Although MIST did not meet the exact endpoint projection of 40% decrease in Migraine, the study is hardly a failure. It was an important first step toward evaluating the impact of PFO closure on Migraine; a step that must be taken if we're to discover how significant the PFO/Migraine connection is and if PFO closure is a viable treatment.

At this time, the future of PFO closure trials is uncertain. NMT discontinued the MIST II trial, citing high expenses. St. Jude Medical discontinued the ESCAPE trial because too fee participants were enrolling for the trial to be valid.

As we continue to follow PFO closure for Migraine, I want to remind readers of an important issue. PFO closure is not a cure. For the vast majority of Migraineurs, it will eliminate only part of their Migraines. PFO closure may eliminate those Migraines triggered by the PFO allowing unoxygenated blood to reach the brain. It cannot prevent Migraines brought on by other triggers.


Press release. "NMT Medical's MIST Study Indicates That Closing a PFO Has an Effect on Migraine." NMT Medical. March 13, 2006.