Cryptogenic strokes, or strokes without an identifiable cause, make up 30-40% of all ischemic strokes.1,2 Some of the etiologies are eventually found to be from cardiac sources, including the presence of a patent foramen ovale (PFO), a congenital defect in the interatrial septum.2,3 A PFO allows for blood to pass directly from the right atrium to the left atrium and has been estimated to be present in up to 15-35% of adults.1,3,4 Stroke due to a PFO is hypothesized to result from either paradoxical embolization or a venous thrombosis circulating through the PFO to the systemic circulation.3 Previous reports have found the presence of a PFO to be significantly associated with a 3-times increased risk of stroke in patients < 55 years of age.4 While younger individuals presenting with a cryptogenic stroke or transient ischemic attack (TIA) are often evaluated for the presence of a PFO, it is not known what the best strategy is to prevent another ischemic stroke or TIA when a PFO is found: do you close the PFO or treat with antiplatelet or antithrombotic therapy?
The CLOSURE I investigators conducted a multicenter, randomized, open-label superiority trial in patients with a cryptogenic stroke or TIA within the last 6 months and evidence of a PFO. The study compared closure of the PFO with a percutaneous device (STARFlex device by NMT Medical) or medical therapy with the primary endpoint being a composite of stroke or TIA during 2 years of follow-up, death from any cause within the first 30 days, and death from neurologic cause from 31 days to 2 years. Secondary end-points included major bleeding, death from any cause, stroke, TIA, and transient neurologic events.2 Enrolled patients could not have another identifiable cause for the stroke. Patients randomized to the closure arm had the device implanted within 1 week and were treated with clopidogrel 75 mg daily for 6 months and aspirin 81 or 325 mg daily for 2 years. The medical therapy arm was treated with warfarin (INR goal 2-3), aspirin 325 mg daily or both, at the discretion of the investigator. The original desired sample size was 1600 patients, but was revised in 2007 to 800 patients due to slow recruitment and new information regarding PFO device closure.2
A total of 909 patients with a mean age of 46 years were evaluated; stroke was the baseline event in 71-73%. The study found no difference in the primary endpoint between closure of the PFO (5.5%) and medical therapy (6.8%, p=0.37). In addition, there was no difference in stroke (2.9% vs. 3.1%) or TIA (3.1% vs. 4.1%) between closure and medical therapy, respectively, with no deaths at 30 days or neurologic deaths at 2 years. The closure device produced successful closure in 86.1% at 6 months, but was associated with more periprocedural major vascular complications (3.2% vs. 0%, p<0.001) and more episodes of atrial fibrillation (5.7% vs. 0.7%, p<0.001) compared to medical therapy. Within 6 months of closure, 1.1% (4/366) were found to have a left atrial thrombus resulting in a stroke in 2 of the 4 patients. There was no difference in major bleeding between the groups.2
The authors concluded that in patients with cryptogenic stroke or TIA with a PFO a closure device ...