Long-term effectiveness and safety of transcatheter closure of patent foramen ovale compared with antithrombotic therapy: A meta-analysis of 6 randomised clinical trials and 3560 patients with reconstructed time-to-event data

AIMS: Although three recent trials showed a significant stroke risk reduction after tPFOc, the impact on pooled evidence deserves attention and individual statistical power is limited. We aimed to pool available randomised clinical trials (RCT) to assess whether tPFOc is more effective and safe than antithrombotic therapy alone (ATA). METHODS AND RESULTS: Major electronic databases and tangential sources were searched and 6 trials (3560 patients) identified. At a median follow-up of 3.6 [2.0-5.2] years (13930 person-years), the risk of stroke was significantly lower after tPFOc compared with ATA (HR 0.28, 95% CI 0.12─0.64, p=0.003). Significant heterogeneity was detected (I2=66.1%), though single trials did not significantly influence the results. Reconstructed time-to-event data revealed that tPFOc benefit accrues approximately after 1 year and persists over time without significant variations (96.4% versus 88.0%; HR 0.25, 95% CI 0.09─0.66, p=0.005; NNT=11). Although results showed a greater benefit in patients <45 years old, male, and with substantial shunt, interaction between subgroups was not significant. Trial sequential analysis showed that accumulated evidence is sufficient. However, tPFOc did not confer protection against transient ischemic attack (TIA; HR 0.69, 95% CI 0.31─1.54, p=0.365) and a significant excess in atrial fibrillation was observed (OR 4.99, 95% CI 1.99─10.10, p<0.001). Major bleeding and migraine were comparable between treatments. CONCLUSIONS: Compared with ATA, tPFOc reduces the risk of stroke at long-term follow-up but no benefit is observed in terms of TIA. Atrial fibrillation is higher after tPFOc, while major bleeding and migraine are comparable between groups.