Abstract
OBJECTIVES: The optimal management approach for patients with cryptogenic stroke and patent foramen ovale (PFO) remains uncertain. Whether medical therapy-using antiplatelet agents or anticoagulants-or transcatheter device closure offers superior protection against stroke recurrence has been a topic of considerable debate. This systematic review aims to assess and compare the effectiveness of these two treatment strategies, incorporating recent studies to provide updated insights on the most effective approach to preventing recurrent cryptogenic stroke. METHODOLOGY: We systematically searched PubMed, Scopus, and Ovid database through December 2024. Eligible studies were randomized controlled clinical trials (RCTs) comparing PFO closure versus medical therapy among patients with cryptogenic stroke. RESULTS: This systematic review analyzed 7 RCTs encompassing 4539 patients with a mean age of 43.6 years, 53.38 % of whom were male. Patient characteristics, including comorbidities such as hypertension, hyperlipidemia, and diabetes mellitus, were well-balanced across groups receiving PFO closure or medical therapy. The primary analysis revealed a significant reduction in stroke incidence with PFO closure compared to medical therapy, with no stroke events in the PFO closure groups of the CLOSE and DEFENSE-PFO trials. Similarly, transient ischemic attack (TIA) incidence was consistently lower in PFO closure groups. All-cause mortality was comparable between groups, underscoring the safety profile of PFO closure. However, PFO closure was associated with a higher incidence of atrial fibrillation. Major bleeding risks varied, reflecting the need for tailored risk assessment. CONCLUSION: PFO closure offers a significant advantage over medical therapy in preventing recurrent cryptogenic stroke and TIA. Nevertheless, the observed increase in atrial fibrillation postclosure highlights the need for additional research to elucidate its long-term implications and to determine whether anticoagulation could benefit specific subsets of patients with PFO and a history of stroke.