CLOSE Trial of PFO Closure Presented at ESOC
May 25, 2017—At ESOC 2017, the European Stroke Organization Conference held May 16–18 in Prague, the Czech Republic, findings from the CLOSE trial were presented by principal investigator Jean-Louis Mas, MD, of the Centre Hospitalier Sainte Anne in Paris, France. The study was funded by the French Ministry of Health.
As summarized in the ESOC presentation, CLOSE assessed whether patent foramen ovale (PFO) closure with a transcatheter device plus (chronic) antiplatelet therapy on one hand, and oral anticoagulants on the other hand, are superior to antiplatelet therapy alone in preventing stroke recurrence in patients aged 16 to 60 years with cryptogenic stroke and PFO with atrial septal aneurysm or PFO with large shunt.
CLOSE is a multicenter, randomized, open-label, three-arm superiority trial with blinded adjudication of outcome events. The trial was designed to enroll 900 patients at 32 sites in France and two sites in Germany, with an 80% statistical power to detect a 50% reduction in the rate of the primary outcome (3.5% per year in the reference arm) in at least one experimental arm with follow-up out to 5 years.
Dr. Mas reported data from 663 patients from December 2008 to December 2014 with follow-up conducted until December 2016. Mean follow-up was 5.3 years (3,544 patient years).
The primary outcome was fatal or nonfatal stroke. The secondary outcome was a composite of ischemic stroke, transient ischemic attack (TIA) or systemic embolism, all-cause mortality, vascular death, success of device implantation, and success of PFO closure. The safety outcomes were major procedural complications and major hemorrhagic complications.
The European Stroke Organization press release reported that key findings from the CLOSE study were that PFO closure significantly reduced the risk of recurrent stroke compared with antiplatelet therapy (hazard ratio [HR], 0.03; 95% confidence interval [CI], 0 to 0.25; P < .001), the difference in risk of recurrent stroke with anticoagulants versus antiplatelet therapy was not significant (HR, 0.43; 95% CI, 0.1–1.5; P = .17), and there was an increased risk of atrial fibrillation with PFO closure, mostly periprocedural and of uncertain significance.
The CLOSE investigators concluded that PFO closure plus long-term antiplatelet therapy reduced the risk of stroke recurrence in patients aged 16 to 60 years with cryptogenic stroke and PFO with an atrial septal aneurysm or PFO with a large shunt, compared with antiplatelet therapy alone. However, the study showed that PFO closure was associated with an increased risk of new-onset atrial fibrillation. Oral anticoagulants did not significantly reduce the risk of stroke recurrence compared with antiplatelet therapy, but there was a trend pointing toward superiority of oral anticoagulants over antiplatelet therapy.