PFO Closure vs. Medical Therapy for Cryptogenic Stroke

Study Questions:

What is the benefit of percutaneous closure of a patent foramen ovale (PFO) after a cryptogenic stroke?


The investigators systematically identified all randomized controlled trials (RCTs) comparing device closure to medical therapy for cryptogenic stroke in patients with PFO. The primary efficacy endpoint was recurrent stroke, analyzed on an intention-to-treat basis. The primary safety endpoint was new-onset atrial fibrillation (AF). Five studies (3,440 patients) were included. A random-effects meta-analysis was performed of the natural logarithm of the hazard ratios (HRs) and their associated standard errors using the restricted maximum likelihood (REML) estimator.


In all, 1,829 patients were randomized to device closure and 1,611 to medical therapy. Across all patients, PFO closure was superior to medical therapy for prevention of stroke (HR, 0.32; 95% confidence interval [CI], 0.13–0.82; p = 0.018; I2 = 73.4%). The risk of AF was significantly increased with device closure (risk ratio [RR], 4.68; 95% CI, 2.19–10.00; p < 0.001; heterogeneity I2 = 27.5%). In patients with large shunts, PFO closure was associated with a significant reduction in stroke (HR, 0.33; 95% CI, 0.16–0.72; p = 0.005), while there was no significant reduction in stroke in patients with a small shunt (HR, 0.90; 95% CI, 0.50–1.60; p = 0.712). There was no effect from the presence or absence of an atrial septal aneurysm on outcomes (p = 0.994).


The authors concluded that in selected patients with cryptogenic stroke, PFO closure is superior to medical therapy for the prevention of further stroke, particularly for patients with moderate-to-large shunts.


This meta-analysis reports that PFO closure after a cryptogenic stroke can significantly reduce the risk of recurrent stroke, and supports the underlying mechanistic plausibility for causation of stroke via paradoxical embolism. With this combination of factors, it appears that, in selected patients, particularly those with moderate-to-large shunts with a cryptogenic stroke and a PFO, device closure reduces future events. Future trials may wish to investigate the role of new oral anticoagulants in this setting rather than antiplatelet therapy as a comparator to device closure to further solidify the role of PFO closure in those with cryptogenic strokes.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Quality Improvement

Keywords: Aneurysm, Anticoagulants, Atrial Fibrillation, Embolism, Paradoxical, Heart Defects, Congenital, Foramen Ovale, Patent, Primary Prevention, Risk, Stroke, Vascular Diseases

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