Objective: To examine the relative impact of three management options in patients less than 60 years old with cryptogenic stroke and a patent foramen ovale (PFO): PFO closure plus antiplatelet therapy, antiplatelet therapy alone, and anticoagulation alone. Design: Systematic review and network meta-analysis (NMA) supported by complementary external evidence Data sources: Medline, EMBASE, and Cochrane CENTRAL. Study selection: Randomised controlled trials (RCTs) addressing PFO closure and/or medical therapies in patients with PFO and cryptogenic stroke. Review methods: We conducted an NMA complemented with external evidence and rated certainty of evidence using the GRADE system. Results: Ten RCTs in eight studies proved eligible (n=4416). PFO closure versus antiplatelet therapy probably results in substantial reduction in ischaemic stroke recurrence (risk difference per 1000 patients over 5 years [RD]: -87, 95% credible interval [CrI] -100 to -33; moderate certainty). Compared with anticoagulation, PFO closure may confer little or no difference in ischaemic stroke recurrence (low certainty) but probably has a lower risk of major bleeding (RD -20, 95% Crl -27 to -2, moderate certainty). Relative to either medical therapy, PFO closure probably increases the risk of persistent atrial fibrillation (RD 18, CI +5 to +56, moderate certainty) and device-related adverse events (RD +36, 95% CI +23 to +50, high certainty). Anticoagulation, compared to antiplatelet therapy, may reduce the risk of ischaemic stroke recurrence (RD -71, 95% CrI -100 to +17, low certainty), but probably increases the risk of major bleeding (RD +12, CrI -5 to +65, moderate certainty). Conclusions: In patients less than 60 years old, PFO closure probably confers an important reduction in ischaemic stroke recurrence compared to antiplatelet therapy alone but may make no difference compared to anticoagulation. PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared to alternatives, anticoagulation probably increases major bleeding.

PFO and Cryptogenic Stroke Data FileThis file contains 4 sheet. PFO vs Medical Therapy, PFO vs Antiplatelet, PFO vs Anticoagulation, and Anticoagulation vs Antiplatelet