Migraine Intervention With STARFlex Technology (MIST)

Summary

Posted: 3/10/2008

Writer: Anthony A. Bavry, M.D., M.P.H.

Description

The goal of this trial was to evaluate closure of patent foramen ovale (PFO) compared with a sham procedure in patients with refractory migraine headache.

Hypothesis

Closure of a PFO with the STARFlex device will be more effective in reducing migraine headache.

Drugs/Procedures Used

After general anesthesia, patients underwent transesophageal echocardiography to assess the interatrial septal anatomy. Patients were then randomized to PFO closure (n = 74) or a sham procedure that consisted of a skin incision (n = 73).

Concomitant Medications

Patients received aspirin (300 mg) and clopidogrel (300 mg) 24 hours prior to the procedure and for 90 days after the procedure at a dose of 75 mg daily for both medications. Patients continued any prophylactic medication that they were on at the start of the trial.

Principal Findings

Of the migraine patients referred for potential study enrollment, a right-to-left shunt from a moderate-to-large PFO was documented by transthoracic echocardiography in 38%. Any type of shunt, including atrial septal defect, was present in 60%. The mean number of migraine attacks in the 30 days prior to the procedure was 4.82 in the closure group and 4.51 in the sham group. No PFO was identifiable in 7% of the closure group. Residual moderate-to-large right-to-left shunt was present in four patients at 6 months. There were more serious procedural-related adverse events in the closure group (atrial fibrillation, n = 2; pericardial tamponade, n = 2; retroperitoneal hemorrhage, n = 1; and chest pain, n = 2).
Three patients in each group reported migraine cessation (p = 1.0). Similarly, for closure versus sham, there was no difference in any of the secondary endpoints; frequency of migraine attacks per month (3.23 vs. 3.52, p = 0.14), total MIDAS headache score (17 vs. 18, p = 0.88), or headache days per 3 months (18 vs. 21, p = 0.79).
No difference in treatment effect was noted, regardless of whether a residual shunt was present at follow-up. Two patient outliers accounted for one-third of the study headache burden. When these patients were removed from analysis, there was a reduction of 2.2 headache days per month in the closure group versus 1.3 days per month in the sham group (p = 0.027).

Interpretation

This was the first randomized sham-controlled trial to study the effect of PFO closure in patients with refractory migraine. An important finding was that among migraine patients referred for analysis, some type of right-to-left shunt was documented in 60% (in 38% due to PFO). The primary outcome, cessation of migraine, occurred in three patients in each group. Secondary outcomes such as frequency of migraines and headache scores were also similar between the two groups.When the two patient outliers were excluded from analysis, a difference was noted in the reduction of headache days favoring PFO closure; however, this finding should only be hypothesis generating since it was a post-hoc analysis.
Failure to detect a difference between treatment groups may have been at least partly explained by lack of adequate power. It is unknown if a longer duration of follow-up to allow for more complete healing of the defect would have also been beneficial. Additionally, patients continued prophylactic medications throughout the trial, which may have made it more difficult for the PFO device to show benefit. Additional trials on the topic are forthcoming.

References:

Dowson A, Mullen MJ, Peatfield R, 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;Mar 3:[Epub ahead of print].

Patent Foramen Ovale and Cryptogenic Stroke in Older Patients

Patent Foramen Ovale and Cryptogenic Stroke in Older Patients

Michael Handke, M.D., Andreas Harloff, M.D., Manfred Olschewski, M.Sc., Andreas Hetzel, M.D., and Annette Geibel, M.D.

NEW ENGLAND JOURNAL OF MEDICINE

Volume 357 — November 29, 2007 — Number 22

ABSTRACT

Background Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age. This association has not been established in patients 55 years of age or older.

Methods We prospectively examined 503 consecutive patients who had had a stroke, and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause. We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomitant atrial septal aneurysm in all patients, using transesophageal echocardiography. We also compared data for the 131 younger patients (<55 years of age) and those for the 372 older patients (55 years of age).

Results The prevalence of patent foramen ovale was significantly greater among patients with cryptogenic stroke than among those with stroke of known cause, for both younger patients (43.9% vs. 14.3%; odds ratio, 4.70; 95% confidence interval [CI], 1.89 to 11.68; P<0.001) and older patients (28.3% vs. 11.9%; odds ratio, 2.92; 95% CI, 1.70 to 5.01; P<0.001). Even stronger was the association between the presence of patent foramen ovale with concomitant atrial septal aneurysm and cryptogenic stroke, as compared with stroke of known cause, among both younger patients (13.4% vs. 2.0%; odds ratio, 7.36; 95% CI, 1.01 to 326.60; P=0.049) and older patients (15.2% vs. 4.4%; odds ratio, 3.88; 95% CI, 1.78 to 8.46; P<0.001). Multivariate analysis adjusted for age, plaque thickness, and presence or absence of coronary artery disease and hypertension showed that the presence of patent foramen ovale was independently associated with cryptogenic stroke in both the younger group (odds ratio, 3.70; 95% CI, 1.42 to 9.65; P=0.008) and the older group (odds ratio, 3.00; 95% CI, 1.73 to 5.23; P<0.001).

Conclusions There is an association between the presence of patent foramen ovale and cryptogenic stroke in both older patients and younger patients. These data suggest that paradoxical embolism is a cause of stroke in both age groups.