SENIOR: Stroke Prevention in the Elderly by Patent Foramen Ovale closuRe vs Anticoagulation (SENIOR)

Patent Foramen Ovale-Related Stroke Management and Outcome: Age-dependent Risk Prediction and Atrial Cardiopathy Study (SENIOR Study)

Patent foramen ovale (PFO) is an important mechanism of embolic stroke of undetermined source (ESUS). Current guidelines recommend PFO closure for high-risk PFO in patients younger than 60 years, and a recent retrospective cohort study from Taichung Veterans General Hospital has shown that closure is effective and safe in older adults; however, the optimal treatment strategy for those >60 years and direct head-to-head comparisons of PFO closure versus direct oral anticoagulants (DOACs) remain insufficient. Robust evidence from a multicenter study combining prospective and retrospective cohorts is warranted.

The SENIOR study is a multicenter observational cohort registry with a combined retrospective and prospective design. The prospective period is from September 15, 2025 to December 31, 2031, and the retrospective period covers January 1, 2013 to September 1, 2025; target sample sizes are 400 (prospective) and 500 (retrospective). We will enroll adults with ESUS and PFO; the prospective arm will focus on patients aged >60 years with PFO related stroke. Treatments will be assigned as PFO closure, standard-dose DOAC, or antiplatelet agents (if DOAC intolerance) by local principal investigator. The primary outcome is recurrent ischemic stroke or transient ischemic attack. Secondary outcomes include 6-month functional outcome, all stroke, and serial comparison of atrial cardiopathy changes. Safety endpoints include peri-procedural adverse events (including newly-onset atrial fibrillation), hemorrhagic stroke, and all caused mortality. Clinical presentation, imaging, cardiac testing, biomarker, and genetic data will be collected for stratified and multivariable analyses.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Elderly; Patent Foramen Ovale (PFO); Embolic Stroke of Undetermined Source
• Intervention / Treatment: Device: PFO closure; Drug: Medication

Detailed Description

Patent foramen ovale-related stroke management and outcome: age-dependent risk prediction and atrial cardiopathy study (SENIOR study) is a multicenter, hybrid retrospective-prospective observational registry designed to address a critical therapeutic gap in the management of embolic stroke of undetermined source (ESUS) associated with patent foramen ovale (PFO), particularly in patients older than 60 years. While randomized controlled trials and contemporary international guidelines support transcatheter PFO closure in carefully selected patients younger than 60 years with high-risk anatomical features, robust evidence remains lacking for older adults, despite the fact that the majority of stroke patients worldwide are now above this age threshold and emerging data suggest that recurrence risk in medically treated elderly patients with PFO may be even higher than in younger cohorts. Furthermore, although anticoagulation-especially with direct oral anticoagulants (DOACs)-has been hypothesized to offer protection comparable to closure in preventing paradoxical embolism, prior trials included very few DOAC-treated patients and did not provide adequately powered head-to-head comparisons between closure and modern anticoagulation strategies. Building upon preliminary real-world data from Taichung Veterans General Hospital demonstrating substantial recurrence reduction with PFO closure in older adults but limited representation of DOAC therapy, the SENIOR registry aims to generate generalizable, decision-relevant evidence by enrolling approximately 900 patients across participating centers, combining retrospective cases (2013-2025) with prospective enrollment (2025-2031). Eligible participants are adults aged 18-90 years with ESUS and confirmed PFO after standardized etiologic work-up, with the prospective arm emphasizing patients ≥60 years who demonstrate high-risk PFO features defined by transcranial Doppler or transesophageal echocardiographic microbubble criteria, atrial septal aneurysm, or long-tunnel anatomy. Treatment allocation is determined through shared decision-making as part of routine care and may include transcatheter PFO closure, standard-dose DOAC therapy, or antiplatelet therapy when anticoagulation is contraindicated, with detailed documentation of clinical rationale to enable rigorous risk adjustment. The primary endpoint is recurrent ischemic stroke or transient ischemic attack, and secondary outcomes include overall stroke events, functional status at one year, safety endpoints such as new-onset atrial fibrillation and major bleeding, and all-cause mortality. In addition to comparative effectiveness analysis using time-to-event modeling and multivariable adjustment, the study incorporates a mechanistic cardiac physiological substudy that longitudinally characterizes atrial cardiopathy and left atrial remodeling through echocardiographic strain, volumetric assessment, and, in closure cases, direct catheter-based left atrial pressure waveform recording to estimate compliance and explore the interaction between structural atrial substrate and paradoxical embolism. By integrating anatomical risk stratification (RoPE and PASCAL classification), age-dependent risk prediction modeling, contemporary antithrombotic strategies, and mechanistic atrial physiology, the SENIOR study seeks to clarify whether advanced age modifies the balance between device-based and pharmacologic stroke prevention, to refine individualized treatment selection for older patients with PFO-related stroke, and to provide the multicenter real-world evidence necessary to inform future randomized trials and guideline evolution.

Study Aims

This is a multicenter, observational cohort study that includes both retrospective and prospective enrollment of patients with patent foramen ovale (PFO)-related stroke. The study aims are:

1. To optimize an age-inclusive risk prediction system for the causal attribution of PFO-related stroke across all age.
2. To compare the effectiveness and safety of transcatheter PFO closure versus medical therapy alone (direct oral anticoagulants [DOAC] or antiplatelet agents if protocol-defined DOAC ineligibility) for prevention of recurrent stroke among patients aged ≥60 years with high-risk PFO.
3. To investigate the role of atrial cardiopathy (AC) in PFO-related stroke, and to further analyze changes in cardiac physiological parameters-such as left atrial (LA) compliance and LA strain-before and after PFO closure and medical therapy alone (optional nested substudy).

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Chi-Sheng Wang, MD; Phone Number: +886933375721; Email: sam7227632@gmail.com
• Study Contact Backup: Name: I-Hui Lee, MD, PhD; Phone Number: 3325 +886-4-23592525; Email: ihui_lee@hotmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital
    • Contact: Chi-Sheng Wang, MD; Phone Number: +886-933375721; Email: sam7227632@gmail.com
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Sung-Chun Tang, MD, PhD
  • Taipei, Taiwan, 100
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: I-Hui Lee, MD, PhD; Email: ihui_lee@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patients with recent embolic stroke of undetermined source and patent foramen ovale (PFO)

Description

Inclusion Criteria:

• Patient or his/her legal representative signs a written informed consent
• Participants who have diagnosed as PFO related stroke
• For patient aged 18-59: patient with high risk PFO feature or RoPE score ≥ 7
• For patient aged 60-90: patient with high risk PFO feature or RoPE score ≥ 4, must include cortical infarct

Exclusion Criteria:

• Follow-up less than 6 months
• Extracardiac right-to-left shunt
• Known stroke mechanism was diagnosed

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Non-elderly, medication; Patient with age < 60 year-old, received standard dose DOAC or antiplatelet if protocol-defined DOAC ineligibility	Drug: Medication; Standard dose direct oral anticoagulant (DOAC) or Antiplatelet if protocol-defined DOAC ineligibility; Unavoidable and non-substitutable severe drug interaction; Newly onset on-label contraindication; Patient refusal of DOAC
Non-elderly, PFO closure; Patient with age < 60 year-old, received PFO closure plus antiplatelet	Device: PFO closure; Transcatheter PFO closure by Amplatzer PFO occluder plus long-term antiplatelet (dual antiplatelet for at least 3 month and life-long single antiplatelet ); Other Names: closure
Elderly, medication; Patient with age ≥ 60 year-old, received standard dose DOAC or antiplatelet if protocol-defined DOAC ineligibility	Drug: Medication; Standard dose direct oral anticoagulant (DOAC) or Antiplatelet if protocol-defined DOAC ineligibility; Unavoidable and non-substitutable severe drug interaction; Newly onset on-label contraindication; Patient refusal of DOAC
Elderly, PFO closure; Patient with age ≥ 60 year-old, received PFO closure plus antiplatelet	Device: PFO closure; Transcatheter PFO closure by Amplatzer PFO occluder plus long-term antiplatelet (dual antiplatelet for at least 3 month and life-long single antiplatelet ); Other Names: closure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent acute ischemic stroke (AIS) or transient ischemic attack (TIA)	AIS: Diagnosed by Neurologist by standard pathway TIA: Hemiplegia, lasting for > 10 minutes and documented by Neurologist	3 year follow-up, at least > 6 months, event-driven

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All strokes and all-cause mortality	TIA, ischemic and hemorrhagic stroke	3 year follow-up, at least > 6 months, event-driven
Functional outcome	modified Rankin scale (mRS) at 6th month after treatment	6 months
Atrial cardiopathy (optional)	changes of LA strain (LA global longitudinal strain [GLS]) and LA volume between baseline and 6~12 months after treatment	12 months
Safety outcome	Peri-procedural adverse events, rocedure related AF (newly-onset AF within 45 days after closure), newly-onset AF (beyond 45 days after closure) in follow-up time, major bleeding, all-cause mortality	3 year follow-up, at least > 6 months, event-driven

Collaborators and Investigators

• Sponsor: Taichung Veterans General Hospital
• Collaborators: National Taiwan University Hospital; Taipei Veterans General Hospital, Taiwan
• Investigators: Principal Investigator: I-Hui Lee, MD, PhD, Taipei Veterans General Hospital, Taiwan; Study Director: Chi-Sheng Wang, MD, Taichung Veterans General Hospital; Study Director: Sung-Chun Tang, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2025
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: elderly; anticoagulation; multi-center; patent foramen ovale; embolic stroke of undetermined source; patent foramen ovale closure
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Stroke; Heart Septal Defects, Atrial; Heart Septal Defects; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ischemic Stroke; Foramen Ovale, Patent; Pharmaceutical Preparations; Investigative Techniques; Technology, Pharmaceutical; Dosage Forms
• Other Study ID Numbers: SENIOR study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Study protocol and informed consent form are available on reasonable request from the principal investigator, I-Hui Lee.

Proposals should be directed to ihui_lee@hotmail.com. To gain access, data requestors will need to sign a data access agreement.

• IPD Sharing Time Frame: following paper publication without end date
• IPD Sharing Access Criteria: on reasonable request from the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No