Clinical trials to assess the relationship between patent foramen ovale and migraine headaches

Abstract

There are 12 observational studies that describe people with episodic migraines, some of whom are refractory to multiple prophylactic medications, who have complete cessation or significant reduction of their headaches and neurological symptoms following closure of a patent foramen ovale (PFO). Since it is difficult to prove without blinding and randomization that the reduction of migraines following PFO closure is due to closure of the right-to-left shunt and not a placebo effect, dramatic observational reports led to the creation of controlled clinical trials to assess the efficacy of PFO closure in patients with refractory migraines. The MIST (Migraine Intervention with STARFlex Technology) trial was the first randomized, double-blinded, sham-controlled trial that was undertaken to evaluate the effect of PFO closure on migraine headaches. Patients were randomized into two groups in a 1:1 ratio to either PFO closure with the STARFlex device or a sham procedure. While the MIST trial confirmed a high prevalence of right-to-left shunt in patients with migraine with aura, no significant difference between the two groups was observed for the primary endpoint of headache cessation or the secondary endpoints of a change in the incidence, severity, frequency or character of migraine or an overall change in the quality of life. However, the negative results of the MIST trial were plagued with controversy due to questions whether the STARFlex device was able to adequately close PFOs. The PREMIUM trial is a double-blind sham-controlled study to evaluate the effect of PFO closure in patients with migraine headaches using the Amplatzer PFO occluder. The PREMIUM trial is currently in progress with all 230 patients having been enrolled and randomized. With the eagerly awaited results of the PREMIUM Trial, it remains to be seen whether PFO closure with the Amplatzer device will demonstrate a different result from the MIST Trial.