PFO closure for the prevention of cerebrovascular events in high-risk individuals: an updated and across-the-board meta-analysis

Abstract

Abstract Introduction Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cerebrovascular events. Despite its seemingly established efficacy, its associated long-term outcomes – including safety – remain unclear. Purpose To ascertain the extent to which PFO percutaneous closure is able to improve long-term clinical outcomes in patients with cryptogenic vascular events. Methods We systematically searched MEDLINE, Embase and Cochrane CENTRAL for randomized controlled trials (RCTs) and observational studies comparing PFO percutaneous closure with antithrombotic therapy, in what concerns recurrent cerebrovascular and serious adverse events, as well as mortality. A composite of stroke and transient ischemic attack (TIA) was the primary endpoint. Data related to RCTs, patients with high-risk PFO features, subjected to PFO closure with the most represented device and with antiplatelet therapy as control were further investigated separately. Study-specific odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random- (DerSimonian-Laird method) or a fixed-effects (Mantel-Haenszel method) model. Results Literature search yielded 2145 references, of which 26 – 8 regarding RCTs – were included. Patients undergoing PFO closure reached 4304, whereas 4180 were treated with antithrombotic therapy. PFO closure was significantly associated with lower stroke/TIA recurrence (OR 0.35 [0.24–0.53], I2=58%). Moreover, such reduction met statistical significance for both stroke (OR 0.34 [0.21–0.54], I2=29%) and TIA (OR 0.53 [0.34–0.82], I2=39%), individually. Subgroup analyses focusing only on RCTs and on studies featuring the most represented device confirmed these trends, while the effects were even more pronounced in patients with high-risk PFO characteristics and in those controlled with antiplatelet therapy. On the other hand, PFO closure was not associated with neither lower all-cause (OR 0.76 [0.46–1.27], I2=0%) nor lower cardiovascular mortality (OR 0.92 [0.37–2.29], I2=0%). Moreover, neither a composite of serious adverse events (SAEs) (OR 1.10 [0.94–1.29], I2=0%) nor major bleeding episodes (OR 0.75 [0.40–1.38], I2=23%) differed significantly between groups. However, PFO closure was associated with increased odds of procedure- or device-related complications (OR 12.94 [5.56–30.13], I2=0%) and atrial fibrillation or flutter (OR 3.35 [1.78–6.30], I2=30%). Conclusion In patients with history of cryptogenic vascular events, when compared with medical management, PFO percutaneous closure is indeed associated with a reduction in the odds of recurrent stroke and TIA. However, mortality seems not to be impacted by this apparently enhanced effect. While general SAEs and major bleeding are comparable between both approaches, PFO closure may bring upon procedure- or device-related complications and increase the odds of atrial fibrillation or flutter. Funding Acknowledgement Type of funding sources: None.