Reevaluating PFO Closure for Migraine
- In a patient-level pooled analysis of patients with migraines both with and without aura, patent foramen ovale (PFO) closure was shown to be safe and reduced the average number of monthly migraine days and attacks compared with medical therapy. The benefit was most pronounced in migraine with frequent aura.
- However, the responder rate (those with ≥50% reduction in migraine attacks) was not significantly different between the 2 groups.
- A randomized controlled trial using a newer device is being conducted that may provide additional data regarding the efficacy of PFO closure for patients with migraine.
PFOs are present in a higher proportion of patients with migraines than in the general population. Multiple studies of PFO closure for stroke showed a high rate of migraine sufferers among participants, many of whom experienced a reduction of migraine days. Two randomized trials were conducted that specifically examined PFO closure for migraine. These studies did not meet their primary endpoints but did meet secondary endpoints. It was felt by pooling the two studies, there may be sufficient power to demonstrate efficacy.
This study's cohort comprised patients who were enrolled in either PRIMA (Percutaneous Closure of Patent Foramen Ovale In Migraine With Aura - A Randomized Prospective Study) or PREMIUM (Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the AMPLATZER PFO Occluder to Medical Management).
This study was a pooled subject-level data analysis of two randomized trials.
The endpoints were mean reduction in migraine days, responder rate (≥50 reduction in monthly migraine attacks), mean reduction in migraine attacks, and complete migraine cessation. The 4 endpoints were given the same importance.
Table 1: PRIMA and PREMIUM
|Ages||21-61 years||18-65 years|
|Migraine Type||With aura||With and without aura|
|Failed Preventive Medications||2||3|
|Screening||PFO on transesophageal echocardiography with bubble study||Transcranial Doppler bubble study with grade 4 or 5 right to left shunt, confirmed by wire crossing during procedure|
|Blinding||Unblinded||Neurologist- and patient-blinded, sham-control procedure|
|Antithrombotic Regimen||3 months clopidogrel
6 months low-dose aspirin
|1 month clopidogrel
6 months 325 mg aspirin
|Closure Completeness||Transesophageal echocardiography at 6 and 12 months if grade 2 or higher shunting remained||Transcranial Doppler at 12 months, grade 2 or less|
|Primary Endpoint||Reduction in migraine days per month||Responder rate (≥50% reduction in migraine attacks)|
Patient characteristics were compared between the two trials. An intention-to-treat analysis was used for the efficacy outcomes. Sub-group analyses were performed looking at age, gender, history of head trauma, mood disorder, palpitations, snoring, steroid use, migraine with aura, and Migraine Disability Assessment and Beck Depression Inventory scores. Safety outcomes were reported for procedural complications for all subjects who received devices (both randomized subjects as well subjects from PREMIUM who had PFO closed after blinding was removed). This analysis was performed "as-treated."
- No significant differences were observed in patient characteristics in the 2 treatment arms.
- Mean reduction in monthly migraine days was 3.1 with PFO closure versus 1.9 with medical therapy alone (p = 0.02).
- Responder rate was 38% with device versus 29% in the control arm (p = 0.13).
- Mean reduction in monthly migraine attacks was -2.0 with device versus 1.4 in the control arm (p = 0.01).
- Complete cessation rate overall was 9% with device versus 0.7 in the control arm (p < 0.001).
- Migraineurs with aura had significant reduction in migraine days and headache cessation (3.2 vs. 1.8 and 11% vs. 1%).
- Migraineurs with frequent aura (aura with >50% of attacks) had significant reductions in all 4 endpoints.
- Procedural complication rates were <1%. There were 4 device-related complications: 1 fatigue, 2 with non-sustained atrial fibrillation, and 1 with syncope.
- The 2 trials had different primary endpoints, so there is inherent bias in interpreting their results together.
- The 2 trials had different populations with respect to minimum number of failed preventive medications (2 vs. 3) and significant differences in multiple characteristics: head trauma, mood disorders, palpitations, steroid use, Migraine Disability Assessment score were all higher in PREMIUM; PRIMA included only migraineurs with aura.
- This was limited to 1-year follow-up; therefore, it is hard to say whether this is durable.
- It is possible that PFOs that were not the cause of the neurovascular event were included because PFOs frequently occur in the general population.
- Mojadidi MK, Kumar P, Mahmoud AN, et al. Pooled Analysis of PFO Occluder Device Trials in Patients With PFO and Migraine. J Am Coll Cardiol 2021;77:667-76.
- Serrano D, Lipton RB, Scher AI, et al. Fluctuations in episodic and chronic migraine status over the course of 1 year: implications for diagnosis, treatment and clinical trial design. J Headache Pain 2017;18:101.
- Tobis JM, Charles A, Silberstein SD, et al. Percutaneous Closure of Patent Foramen Ovale in Patients With Migraine: The PREMIUM Trial. J Am Coll Cardiol 2017;70:2766-74.
- Mattle HP, Evers S, Hildick-Smith D, et al. Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial. Eur Heart J 2016;37:2029-36.
Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Noninvasive Imaging, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Quality Improvement, Echocardiography/Ultrasound, Invasive Cardiovascular Angiography and Intervention
Keywords: Prospective Studies, Fibrinolytic Agents, Foramen Ovale, Patent, Echocardiography, Transesophageal, Intention to Treat Analysis, Atrial Fibrillation, Migraine with Aura, Aspirin, Data Interpretation, Statistical, Follow-Up Studies, Migraine Disorders, Stroke, Headache, Syncope, Epilepsy, Fatigue, Craniocerebral Trauma, Steroids
< Back to Listings