Patent foramen ovale closure versus medical therapy alone in elderly patients with cryptogenic stroke: a systematic review and meta-analysis.

INTRODUCTION

Current guideline recommendations from American Heart Association/American Stroke Association (AHA/ASA) strongly favor percutaneous patent foramen ovale closure (PFOC) over medical therapy alone only for younger patients aged 18–60 years with a prior cryptogenic stroke (CS). However, for patients aged ≥ 60 years, evidence remains limited and uncertain.

OBJECTIVE

To evaluate the efficacy and safety of PFOC with background medical therapy compared with medical therapy alone in elderly (≥ 60 years) patients with CS.

METHODS

We systematically searched PubMed, Embase, and Cochrane Library from inception to August 2025. We restricted inclusion in this study to articles that met all the following eligibility criteria: (1) RCTs and comparative retrospective or prospective observational studies; (2) that enrolled elderly (≥ 60 years) participants diagnosed with CS. The primary outcome was defined as recurrent IS or TIA in the follow-up after PFOC or initiation of medical therapy alone. The safety outcomes were defined as: (1) all-cause mortality in the follow-up, (2) development of new onset atrial fibrillation (AF)/flutter and (3) major bleeding events. All statistical analyses were performed using R Studio version 4.3.2. We employed a risk ratio (RR) with 95% confidence intervals (CIs) as the measure of effect size to report binary outcomes with p-value lower than 0.05 to achieve statistical significance.

RESULTS

Seven observational studies were included. Publication years ranged from 2012 to 2025. A total of 6,725 patients were enrolled including 1,636 (24.3%) in the PFOC group and 5,089 (75.7%) in the medical therapy alone group. PFOC showed statistically significantly lower rates of recurrent ischemic stroke or TIA (RR 0.49; 95% CI: 0.35–0.67; p < 0.001; I² = 3.2%) and all-cause mortality compared to medical therapy alone (RR 0.39; 95% CI: 0.18–0.87; p = 0.022; I² = 22.0%). PFOC showed no statistically significant difference compared to medical therapy alone regarding new onset atrial fibrillation or atrial flutter (RR 1.38; 95% CI: 0.60–3.15; p = 0.448; I² = 66.3%) and major bleeding (RR 0.99; 95% CI: 0.44–2.24; p = 0.977; I² = 19.9%).

CONCLUSION

This meta-analysis findings suggest that selected patients aged ≥ 60 years with CS may derive benefit from PFOC, with reductions in recurrent cerebrovascular ischemic events and mortality, without an excess risk of new onset AF/flutter or major bleeding compared to medical therapy alone.