Findings Published From CLOSE Trial of PFO Closure After Stroke

September 19, 2017—Principal Investigator Jean-Louis Mas, MD, et al published findings from the CLOSE trial in The New England Journal of Medicine (NEJM; 2017;377:1011–1021). CLOSE investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from patent foramen ovale (PFO) closure or anticoagulation, as compared with antiplatelet therapy.

The investigators concluded that among patients who had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. However, PFO closure was associated with an increased risk of atrial fibrillation.

The findings were first presented in May at ESOC 2017, the European Stroke Organization Conference in Prague, the Czech Republic. The study was funded by the French Ministry of Health.

As summarized in NEJM, the multicenter, randomized, open-label CLOSE trial was composed of 663 patients, ages 16 to 60 years, who had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt. These patients were assigned in a 1:1:1 ratio to transcatheter PFO closure plus long-term antiplatelet therapy, antiplatelet therapy alone, or oral anticoagulation (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3).

The primary outcome was the occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. Patients were followed for a mean of 5.3 ± 2 years.

In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0–0.26; P < .001). Procedural complications from PFO closure occurred in 14 patients (5.9%).

The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs 0.9%; P = .02). The number of serious adverse events did not differ significantly between the treatment groups (P = .56). In the analysis of randomization groups 1 and 3, stroke occurred in three of 187 patients assigned to oral anticoagulants and in seven of 174 patients assigned to antiplatelet therapy alone, reported the investigators in NEJM.