PFO Closure: CLOSURE.

T he optimal secondary prevention strategy in patients presenting with a cryptogenic stroke or transient ischemic attack (TIA) and a patent foramen ovale (PFO) is uncertain. In the United States, closure of a PFO using a percutaneous transcatheter device is currently considered investigational by the Food and Drug Administration. Nonetheless, many patients in this setting are treated off-label with devices that are approved for the closure of secundum atrial septal defects. There are also no definitive data about the use of medical therapy for secondary stroke prevention in this patient population. We evaluated the potential benefit of device closure of a PFO in this setting in CLOSURE I (evaluation of the STARFlex Septal Closure System in patients with a stroke and/or TIA because of presumed paradoxical embolism through a PFO). 1 Methods CLOSURE I was a prospective, multicenter, randomized, open-label, 2-arm superiority trial. The trial was sponsored by NMT Medical, Inc. The protocol was designed by the Executive Committee in consultation with the Food and Drug Administration, and was approved by the institutional review board at each participating site. Methodological details have been previously published. Subjects were eligible for randomization if they were aged between 18 and 60 years, had had an ischemic stroke or TIA within the previous 6 months, and had evidence of a PFO with right to left shunting documented by a transesophageal echocardiogram. Exclusion criteria included any identified potential source of ischemic stroke or TIA other than the PFO. Eligible patients were randomly assigned in a 1:1 ratio to either device therapy or medical therapy. Randomization was stratified by study site and by presence or absence of an atrial septal aneurysm. Patients assigned to device therapy underwent percutaneous closure of their PFO with the STARFlex device (NMT Medical, Inc). After the procedure, all patients were prescribed clopidogrel 75 mg daily for 6 months and aspirin 81 or 325 mg daily for 2 years. Patients assigned to medical therapy were treated at the discretion of the site principal investigator with warfarin (target international normaliza-tion ratio, 2.0–3.0), aspirin (325 mg), or both. Follow-up evaluations were planned at 1, 6, 12, and 24 months. A transesophageal echocardiogram was obtained at the 6-month visit for patients in the device arm. The primary end point was a 2-year composite, including stroke, TIA, all-cause mortality for the first 30 days, and neurological mortality after 30 days. Secondary end points included major bleeding, …