Device Closure of Patent Foramen Ovale or Medical Therapy for Cryptogenic Stroke: The CLOSURE I Trial

Abstract

CLOSURE I was the first randomized clinical trial that investigated the use of medical therapy versus medical therapy combined with transcatheter patent foramen ovale (PFO) closure, for the treatment of stroke or transient ischemic attack (TIA). The study included patients between the ages of 18 and 60 who were diagnosed with a cryptogenic stroke or TIA with evidence of a PFO by transesophageal echo. Patients with other identifiable causes for ischemic stroke or TIA, such as carotid artery stenosis, complex aortic arch atheroma, significant left ventricular dysfunction or aneurysm, or atrial fibrillation were excluded. The justification for performing this trial was that observational studies in patients who had suffered a cryptogenic stroke and underwent PFO closure, appeared to have a much lower recurrence rate of stroke compared to patients remained on medical therapy without PFO closure 909 patients were randomized in a 1:1 ratio to either percutaneous PFO closure with the STARFlex Septal Occluder plus antiplatelet therapy with aspirin and clopidogrel, or medical therapy alone with aspirin, warfarin or a combination of both. The primary endpoint was stroke and/or TIA, all-cause mortality within the first 30 days, and death from a neurological cause occurring between 31 days and 2 years. Secondary endpoints were all-cause mortality, stroke, TIA, significant bleeding, and other transient neurologic events of undetermined etiology. After a 2-year follow up, there were no statistical differences in the primary and secondary outcomes when comparing the Closure group versus the Medical Therapy group in both the intention-to-treat and per-protocol populations. The study was heavily criticized for its use of a suboptimal device that resulted in incomplete PFO closure in a large fraction of patients, as well as an increased risk of atrial fibrillation and thrombogenesis compared to the Medical Therapy group.