Background—Patent foramen ovale (PFO) is associated with stroke, but there are no randomized studies to evaluate the efficacy of antithrombotic therapies.

Methods and Results—The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings in patients randomly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study. In this study, 630 stroke patients were enrolled, of whom 312 (49.5%) were randomized to warfarin and 318 (50.5%) to aspirin. Of these, 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes. End points were recurrent ischemic stroke or death. PFO was present in 203 patients (33.8%). There was no significant difference in the time to primary end points between those with and those without PFO in the overall population (P=0.84; hazard ratio 0.96; 95% CI 0.62 to 1.48; 2-year event rates 14.8% versus 15.4%) or in the cryptogenic subset (P=0.65; hazard ratio 1.17; 95% CI 0.60 to 2.37; 2-year event rates 14.3% versus 12.7%). There was no significant difference among those with no, small, or large PFO (P=0.41 for small PFO and P=0.16 for large PFO; 2-year event rates for no, small, and large PFO, 15.4%, 18.5%, and 9.5%, respectively). There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm (P=0.84; 2-year event rates 14.5% versus 15.9%). In patients with PFO, there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin (P=0.49; hazard ratio 1.29; 95% CI 0.63 to 2.64; 2-year event rates 16.5% versus 13.2%).

Conclusions—On medical therapy, the presence of PFO in stroke patients did not increase the chance of adverse events regardless of PFO size or the presence of atrial septal aneurysm.