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J Am Heart Assoc. 2018 Jun 17;7(12). pii: e008356. doi: 10.1161/JAHA.117.008356.

Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta-Analysis, and New Insights From the CLOSE Study.

Turc G1,2,3,4, Calvet D1,2,3,4, Guérin P5,6, Sroussi M2,7, Chatellier G2,8,9, Mas JL10,2,3,4; CLOSE Investigators.

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Department of Neurology, Hôpital Sainte-Anne, Paris, France.
Université Paris Descartes Sorbonne Paris Cité, Paris, France.
NSERM U894, Paris, France.
DHU Neurovasc, Paris, France.
Department of Cardiology, INSERM UMR 915 Institut du Thorax, Nantes, France.
Institut du Thorax, Centre Hospitalier Universitaire de Nantes, Nantes, France.
Department of Cardiology, Cochin Hospital APHP, Paris, France.
Epidemiology and Clinical Research Unit, Georges Pompidou European Hospital APHP, Paris, France.
INSERM CIC 1418, Paris, France.
Department of Neurology, Hôpital Sainte-Anne, Paris, France



We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO-associated cryptogenic stroke.


We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random-effects meta-analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17-0.79; I2=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11-0.70; I2=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43-1.47; I2=12%). Major complications occurred in 2.40% (95% CI, 1.03-4.25; I2=77%) of procedures. New-onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37-7.89; I2=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00-1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05-0.63; I2=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.


PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle-aged patients. PFO closure was associated with an increased risk of atrial fibrillation.


anticoagulation; patent foramen ovale; patent foramen ovale closure; stroke

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