LAUSR

BACKGROUND In patients with patent foramen ovale (PFO)-associated stroke, the presence of large shunt or atrial septal aneurysm (ASA) has been suggested to convey a high risk of stroke recurrence. OBJECTIVES The purpose of this study was to assess the respective influence of PFO size and ASA status on stroke recurrence under medical therapy in patients with recent PFO-associated stroke without alternative cause. METHODS The authors pooled individual patient data from 2 prospective observational studies and the medical arms of 2 randomized trials, in which shunt size and ASA status was assessed by independent reading of echocardiographic images. Associations between PFO anatomical features and recurrent ischemic stroke were assessed by mixed effects Cox models. RESULTS Of 898 patients (mean age 45.3 years), 178 (19.8%) had ASA with large PFO, 71 (7.9%) ASA with nonlarge PFO, 397 (44.2%) large PFO without ASA, and 252 (28.1%) nonlarge PFO without ASA. Over a median follow-up of 3.8 years (interquartile range: 2.6 to 5.5 years), 47 (5.2%) patients experienced a recurrent stroke. There was a heterogeneity across studies for the association between PFO size and stroke recurrence (pinteraction = 0.01). In a model accounting for age, hypertension, antithrombotic therapy, and PFO anatomy, ASA was independently associated with recurrent stroke (adjusted hazard ratio: 3.27; 95% confidence interval: 1.82 to 5.86; p < 0.0001), whereas large PFO was not (average adjusted hazard ratio across studies: 1.43; 95% confidence interval: 0.50 to 4.03; p = 0.50). CONCLUSIONS In patients with PFO-associated stroke, ASA is a more important predictor of recurrent stroke than shunt size. These results can help to better identify those patients with a high risk of stroke recurrence under medical therapy who may derive the most benefit from PFO closure. (Patent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke Recurrence [CLOSE]; NCT00562289) (Device Closure versus Medical Therapy in Patients with Cryptogenic Stroke and High-Risk Patent Foramen Ovale [DEFENSE-PFO]; NCT01550588).