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Around 15% of all individuals have a patent foramen ovale (PFO) in autopsy studies. For some patients with ischemic stroke or transient ischemic attack (TIA), PFO has been implicated as an etiology of paradoxical embolism to the brain. However, whether these patients should be treated with antithrombotic medications or closure of their PFO remains unclear. Three fairly recent large trials of endovascular PFO closure in patients with cryptogenic stroke failed to show any benefit compared with standard antithrombotic regimens. However, the search continues for subgroups of patients who might benefit from closure of PFO following stroke, and hence the results of a recent trial reported by Mas and colleagues (2017) were eagerly anticipated.

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The authors performed a multicenter, open-label, randomized trial at 34 sites in Europe. Particularly high-risk patients identified in other stroke and PFO trials have been those with large PFOs, those with an associated atrial septal aneurysm (ASA), and those who were of younger age. Therefore entry criteria into this trial included patients age 16–60 who had an ischemic stroke in the past 6 months without another identifiable cause other than a large PFO or one with an associated ASA. Extensive workup to exclude other causes of stroke was negative in all patients, although long-term cardiac monitoring looking for atrial fibrillation was not performed.

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Patients were randomly assigned to PFO closure with long-term antiplatelet therapy, antiplatelet therapy alone, or anticoagulation alone. Patients undergoing PFO closure with 1 of 11 implantable devices were treated first with dual antiplatelet medications for 3 months and then with single antiplatelet medications for the rest of the trial. Neurologists aware of the treatment assignment evaluated patients at 2 months, 6 months, and then every 6 months until the end of the trial. The primary outcome examined was the occurrence of fatal or nonfatal stroke.

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A total of 664 patients were enrolled in the study, and baseline characteristics were not significantly different between the groups. The mean duration of follow-up was between 5 and 5.4 years in the various groups. Using an intention-to-treat approach, 0 patients in the PFO closure group had a stroke during the trial compared with 14 in the antiplatelet-only group (hazard ratio [HR], 0.03; 95% confidence interval [CI], 0–0.26; p < .001). A secondary outcome of stroke, TIA, or systemic embolism was significantly less common in the closure group compared with those treated with antiplatelet medications alone (3.4% vs 8.9%; HR, 0.39; 95% CI, 0.16–0.82; p = .01). Comparisons between the anticoagulation and antiplatelet groups were not adequately powered for efficacy, but there were more strokes seen in the antiplatelet group (4.0% vs 1.6%).

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Major procedural complications were observed in 5.9% of the closure group, including a significantly higher risk of the development of atrial fibrillation. The rate of effective PFO closure was 93% at follow-up echocardiography.

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This important trial, which was accompanied by two other positive trials using a similar approach in the same issue of the journal, demonstrates that some patients with PFO and stroke should indeed consider closure for secondary prevention. It is clear that while PFO closure should not occur in all patients with stroke and PFO, there is likely a subset of patients that may benefit. It now remains up to doctors and their patients to have a discussion regarding the risks and benefits of closure in individual cases, and up to the stroke community to educate colleagues as to which patients should be offered this intervention.

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Mas  J-L  et al.: Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke.. N Engl J Med 377:1011, 2017
[PubMed: 28902593]