Closure of PFO Does Not Reduce Migraine Frequency
Closure of PFO Does Not Reduce Migraine Frequency
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD Dr. Boyle is Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Boyle reports no financial relationships relevant to this field of study.
Source: Dowson A, et al Migraine Intervention with STARFlex Technology (MIST) Trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation. 2008;117:1397-1404.
Observational studies of percutaneous device closure of patent foramen ovale (PFO) have suggested that the incidence of migraines is reduced after this procedure. The hypothesis is that vasoactive substances that are normally cleared by the lung can pass through a right-to-left shunt via a PFO and reach the brain, causing migraine with aura. Dowson and colleagues performed a randomized, controlled trial to assess the efficacy of PFO closure in reducing the incidence of migraine with aura.
Previous studies performed PFO closure to prevent stroke or decompression illness, and the effects on migraines were anecdotal. Dowson et al enrolled only patients with frequent, disabling, and drug-resistant migraine with aura. Patients were recruited from headache clinics or by self-referral through the trial website. Headache inclusion criteria included at least five episodes per month and at least seven migraine-free days per month, as well as failure of at least two classes of preventive medication. Eligible patients then underwent transthoracic echocardiography (TTE) with bubble study to confirm a moderate or large right-to-left shunt (RLS). Patients who consented were loaded with aspirin and clopidogrel and brought to the cardiac catheterization lab, where randomization was performed; 147 patients were randomized: 74 to PFO closure and 73 to sham procedure (skin incision only). Patients and referring physicians remained blinded. Follow-up was performed by headache specialists, and involved headache diaries, Headache Impact Test, and quality-of-life questionnaires. The primary end point was complete cessation of migraines. Secondary end points were changes in frequency, severity, and characteristics of migraine, as well as quality of life. All patients received 90 days of aspirin and clopidogrel and were followed up for six months.
Results: There was no difference between groups in the primary or secondary end points. Only three patients in each group had complete cessation of migraine. Frequency of migraine attacks per month reduced from 4.9 ± 2.4 to 3.3 ± 1.8 in the PFO closure group and from 4.6 ± 2.2 to 3.6 ± 2.1 in the sham group (P = 0.13). Importantly, four patients in the treatment group had persistent moderate or large atrial shunts at final follow-up; however, there was no difference in outcomes between those with residual shunts vs those with no residual shunt. In the absence of any difference in the predefined end points, Dowson et al performed an exploratory analysis. They found two outliers in the PFO closure group that were responsible for more than a third of all migraine headache days. When these patients were excluded from the analysis, there was a 37% reduction in number of headache days per month from 6.7 to 3.8 in the closure group, compared to 26% reduction in the sham operation group from 5.0 to 3.7 days/month (P = 0.027). Dowson et al concluded that there is a high incidence of PFO in severe migraine patients, but initial results of percutaneous closure show only a modest reduction in attacks.
Commentary
In the accompanying editorial, a number of limitations of the study were highlighted. There were a number of procedural complications in the PFO closure group: two pericardial effusions (one of which caused tamponade and required drainage), one retroperitoneal bleed, two patients developed atrial fibrillation. This was a higher than expected procedural complication rate. In addition, no PFO could be found or crossed in five of 74 patients. This was also a higher than expected rate, and the cause remains unclear. It may demonstrate that this patient group has more complex or multiple shunt levels, or that the shunt occurs in the lungs.
Dowson et al are to be commended for their rigorous trial design, including the incorporation of a sham-procedure arm. This strengthens any conclusions that are drawn from the study; however, they state in the discussion that the study was underpowered to detect the primary or secondary end points, as the trial power calculations were based on observational, retrospective data, suggesting much larger changes in migraine frequency. Dowson et al conclude that "although no significant effect was found for the primary or secondary end points, the exploratory analysis supports further investigation. MIST emphasizes the critical importance of blinding in the evaluation of novel interventions." Larger randomized trials to extend these findings are currently underway in the United States and Europe.
Dowson and colleagues performed a randomized, controlled trial to assess the efficacy of PFO closure in reducing the incidence of migraine with aura.Subscribe Now for Access
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