Patent foramen ovale closure vs medical therapy in secondary prevention of stroke and TIA: A systemic review and meta-analysis

Abstract

Importance: Percutaneous Patent Foramen Ovale (PFO) closure reduces recurrent ischemic stroke and transient ischemic attack (TIA) in cryptogenic stroke patients. The publication of additional studies and the inclusion of a larger patient population necessitate an updated analysis to evaluate its efficacy and safety compared to medical therapies and across different age groups.

Objective: To compare the efficacy and safety of PFO closure versus medical therapy for the secondary prevention of stroke and TIA.

Data sources: A systematic literature search was performed using PubMed, CENTRAL, and EMBASE from inception to August 2024.

Study selection: Included studies involved adults (≥18) with ischemic neurological events and confirmed PFO, comparing percutaneous PFO closure to medical therapy, and reporting outcomes of interest.

Data extraction and synthesis: Data were independently extracted by 2 reviewers following PRISMA guidelines. Quality assessment utilized the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for observational studies. Odds ratios (ORs) with 95 % confidence intervals (CIs) were pooled using random or fixed effects models. Subgroup analyses were conducted based on age, shunt size, and presence of ASA.

Main outcome(s) and measure(s): Primary outcomes included recurrent ischemic stroke and/or TIA, and all-cause mortality. The safety outcomes were atrial fibrillation/flutter and major bleeding.

Results: A total of 32 studies (6 randomized controlled trials and 26 observational studies) comprising 16,698 patients met the inclusion criteria. PFO closure significantly reduced the risk of recurrent ischemic stroke/TIA compared to medical therapy (OR 0.52, P < 0.001), with greater benefits over antiplatelet therapy (OR 0.33, P < 0.001) and anticoagulant therapy (OR 0.42, P < 0.001). Additionally, PFO closure reduced all-cause mortality (OR 0.49, P < 0.001) but was associated with an increased risk of atrial fibrillation (OR 3.45, P < 0.001). Subgroup analyses demonstrated similar significant benefits in recurrent stroke prevention for both older patients (≥60 years, OR 0.39) and younger patients (<60 years, OR 0.56).

Conclusions and relevance: This meta-analysis suggests that PFO closure is associated with lower risk of recurrent ischemic events and all-cause mortality compared to medical therapy. However, outcomes such as TIA and mortality were predominantly observed in observational studies. These findings are hypothesis-generating and support further investigation in selected patient populations.

Keywords: Medical therapy; Meta-analysis; Patent foramen ovale closure; Recurrent neurological ischemic events; Stroke; TIA.