Currently submitted to: JMIR Research Protocols
Date Submitted: Jun 8, 2026
Open Peer Review Period: Jun 8, 2026 - Aug 3, 2026
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Patent Foramen Ovale Closure Outcomes in Patients of Advanced Age (PFO-COPA): Protocol for a Multicenter Retrospective Cohort Study
ABSTRACT
Background:
Patent foramen ovale (PFO) is a common cardiac abnormality associated with paradoxical embolism and ischemic stroke. Randomized trials have demonstrated the benefit of percutaneous closure patients below 60 years with cryptogenic stroke, but nearly all excluded individuals aged ≥60 years, leaving a critical evidence gap in older populations where competing stroke mechanisms are prevalent. There is currently no dedicated, validated framework to guide closure decisions in this age group. Consequently, clinical practice remains highly variable, and closure decisions are often made based on extrapolation from younger cohorts rather than robust evidence.
Objective:
To evaluate the effectiveness and safety of PFO closure compared with medical therapy in patients aged ≥60 years with cryptogenic stroke and confirmed PFO.
Methods:
This multicenter retrospective cohort study will include consecutive patients aged ≥60 years with imaging-confirmed ischemic stroke, a confirmed PFO, and no alternative definite stroke etiology after standard diagnostic evaluation, who underwent either percutaneous PFO closure or medical therapy between 2015 and 2025. Outcomes will be collected through standardized chart review and entered into a centralized Research Electronic Data Capture (REDCap) database. The primary outcome is risk of recurrent ischemic stroke. Secondary outcomes include major bleeding, new-onset atrial fibrillation, device-related complications, and mortality. Time-to-event analyses, Cox regression, and propensity score methods will be used to adjust for confounding.
Results:
As of May 2026, sixty-five centers from nine countries have formally committed to participate in the study. Each site is in the process of securing IRB approval and executing data use agreements. A standardized variable dictionary has been distributed to all centers to ensure consistency in data collection. Data entry into the centralized REDCap database is scheduled to begin in August 2026. Participating centers are encouraged to propose independent research questions leveraging the pooled dataset; to date, twenty three project titles have been submitted by investigators. These proposals will be evaluated once sufficient data accrual has been achieved, with prioritization based on feasibility and data availability.
Conclusions:
The PFO COPA study will generate the most comprehensive real world evidence to date on PFO closure in adults aged ≥60 years. By evaluating both effectiveness and safety in this understudied age group, the study will fill a major evidence gap and help guide clinical decision making. Ultimately, these findings may inform future guideline updates and lay the groundwork for prospective multicenter trials focused specifically on older adults. Clinical Trial: N/A
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