Doctors Peter Wilmshurst and Andrew Dowson, co-primary investigators of MIST, jointly presented the results at the American College of Cardiology's 55th Annual Scientific, Late-Breaking Clinical Trials Sessions on March 13, 2006. 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, which screened 432 migraine with aura patients for a PFO, 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 shunt is 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.

Findings*
1. Only a small minority of migraine sufferers experience migraine with aura.

2. Observational studies have suggested that the prevalence of right to left cardiac shunt is higher in patients with migraine with aura than patients with migraine without aura and those who do not suffer from migraine.

3. Retrospective studies of patients with decompression sickness or stroke have suggested that closure of shunts are followed by short term improvement of migraine in some cases.

4. Adoption of new technology involves appraisal of its costs, risks and benefits from information obtained from well designed, prospective trials over a relevant time scale.

5. A recent trial (Migraine intervention with StarFlex technology) has reported on patients with migraine with aura who failed to respond to two preventative treatments. In the 90 days after the healing phase of a PFO repair, a target of 40% elimination of migraine at six months in the treatment group was not achieved. There was a significant but modest reduction in migraine burden in the 90 days following healing measured as the number of headaches multiplied by time in hours of each headache. (37% reduction in the intervention group compared with 17% reduction in the control group who received a sham procedure). These results can not be generalised to migraine patients who do not have aura.

6. Further studies are underway that include investigation of outcomes over longer time periods and larger groups of patients.

7. On the basis of the current evidence, the cost and risk of this intervention are not commensurate with the benefits received. Poorly controlled patients who have high impact migraine should be assessed by a practitioner with a special interest and experience in migraine to explore alternative therapeutic options.

*These findings are published on the British Association for the Study of Headache website.