Percutaneous Closure of PFO in Patients With Migraine

Study Questions:

What is the efficacy of percutaneous patent foramen ovale (PFO) closure as a therapy for migraine with or without aura?


The PREMIUM (Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management) was a double-blind study investigating migraine characteristics over 1 year in subjects randomized to medical therapy with a sham procedure (right heart catheterization) versus medical therapy and PFO closure with the Amplatzer PFO Occluder device (St. Jude Medical, St. Paul, MN). Subjects had 6-14 days of migraine per month, had failed ≥3 migraine preventive medications, and had significant right-to-left shunt defined by transcranial Doppler. Primary endpoints were responder rate defined as 50% reduction in migraine attacks and adverse events. Secondary endpoints included reduction in migraine days and efficacy in patients with versus without aura.


Of 1,653 subjects consented, 230 were enrolled. There was no difference in responder rate in the PFO closure (45 of 117) versus control (33 of 103) groups. One serious adverse event (transient atrial fibrillation) occurred in 205 subjects who underwent PFO closure. Subjects in the PFO closure group had a significantly greater reduction in headache days (–3.4 vs. –2.0 days/month, p = 0.025). Complete migraine remission for 1 year occurred in 10 patients (8.5%) in the treatment group versus 1 (1%) in the control group (p = 0.01).


The authors concluded that PFO closure did not meet the primary endpoint of reduction in responder rate in patients with frequent migraine.


This trial of PFO closure to prevent migraine did not meet the primary endpoint of a superior 50% or greater reduction in migraine attacks compared with sham control. However, this trial did meet the non-prespecified, secondary endpoint of significant reduction in headache days after PFO closure for subjects with or without aura. This observation underscores the importance of having an adequate sham control and double-blinding in clinical trials of device interventions, as was also evident in the recently reported ORBITA (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias

Keywords: Atrial Fibrillation, Cardiac Catheterization, Foramen Ovale, Patent, Headache, Heart Defects, Congenital, Incidence, Migraine Disorders, Migraine with Aura, Primary Prevention, Septal Occluder Device

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