The PRIMA (Percutaneous closure of patent foramen ovale in migraine with aura) study indicates that percutaneous closure of patent foramen ovale is associated with a significant reduction in migraine with aura days compared with medical therapy. However, it does not reduce total migraine days.
Presenting the data at the Transcatheter Cardiovascular Therapeutics (TCT) meeting (13–17 September, Washington, DC, USA), David Hildick-Smith (Sussex Cardiac Centre, Brighton & Sussex University Hospital Trust, Brighton, UK) reported that observational studies indicate that percutaneous closure of patent foramen ovale is associated with a high rate of resolution of incidental migraine. He explained one hypothesis for this finding was that eliminating the right-to-left shunt through percutaneous closure may reduce some of the chemical or physical triggers for migraine. The aim of the PRIMA study, therefore, was to evaluate whether percutaneous closure of patent foramen ovale was effective at reducing migraine headache in patients with migraine with aura who were refractory to medical treatment. The primary endpoint was the reduction in migraine days one year after randomisation, which Hildick-Smith stated was calculated by subtracting the mean number of migraine days in months 10 to 12 of the study from the mean number of migraine days during the three-month roll-in phase.
Of 705 patients who consented to be involved in the study, only 107 were enrolled. The reasons for not enrolling patient included right-to-left shunt not being demonstrated (303 patients), patent foramen ovale not confirmed (73), patients not willing to consent (37), and being responsive to preventative medication (36). Of those enrolled, 53 were randomised to receive percutaneous closure with the Amplatzer PFO Occluder (St Jude Medical)—of whom, 41 actually received the device—and 54 were randomised to receive medical management. At the 12-month follow-up point, data were available for 40 of the percutaneous closure patients and 43 of the medical therapy patients.
Hildick-Smith said that there was a “numerical but not statistically significant” difference between the two groups in the primary endpoint: the mean reduction in total migraine days in the percutaneous closure was 2.9 (8 days at baseline to 5.1 days at months 10–12) compared with 1.7 in the medical therapy group (8.3 days at baseline to 6.5 days at months 10–12); p=0.17. However, he added that percutaneous closure was associated with a “highly statistically significant” reduction in migraine with aura days: a mean reduction of 2.4 days (4.1 days at baseline to 1.7 days at months 10–12) vs. a reduction of 0.6 days (4 days at baseline to 3.4 days at months 10–12 ) for medical therapy; p=0.01. Furthermore, percutaneous closure significantly increased the responder rate (37.5% vs. 14.6% for medical therapy; p=0.02) and significantly increased freedom from migraine (10% vs. 0%, respectively; p<0.05).
Hildick-Smith concluded: “40% of device closure patients had headache burden reduced by ≥50%, 10% of closure patients became migraine free, and no fewer than 40% of closure patients became free of migraine with aura.” He added: “If I was patient whose life was blighted by migraine with aura, I would be really interested in these results and would think that this therapy warranted further investigation.”
The main aim of percutaneous closure of patent foramen ovale is to reduce the risk of recurrent stroke. However, two studies (RESPECT and the PC Trial) failed to show a significant difference between percutaneous closure of patent foramen ovale and medical therapy in the prevention of stroke in patients with cryptogenic stroke (although RESPECT did show a significant benefit with percutaneous closure in an as-treated analysis). According to Hildick-Smith, the decision to use percutaneous closure of patent foramen ovale purely to reduce migraine with aura (rather than to reduce the risk of stroke) would a “decision for individual patients”. He told Cardiovascular News: “If your migraine with aura is highly disruptive, and other treatments have not been successful, then I would have thought patent foramen ovale closure was certainly worth looking at.”