What is the evidence for patent foramen ovale (PFO) closure in the setting of cryptogenic stroke?

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Last updated: April 30, 2025View editorial policy

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From the Guidelines

Patent foramen ovale (PFO) closure is recommended for selected patients with cryptogenic stroke, particularly those under 60 years with moderate-to-large shunts and no other identified stroke cause, as it reduces recurrent stroke risk compared to medical therapy alone. The evidence from recent randomized controlled trials, such as the CLOSE trial 1, REDUCE trial 1, and RESPECT trial 1, demonstrates that PFO closure plus antiplatelet therapy is superior to medical therapy alone in preventing stroke recurrence. The benefit is most pronounced in patients with high-risk PFO features, such as large shunts or associated atrial septal aneurysms.

The CLOSE trial 1 showed that PFO closure resulted in a significant reduction in stroke recurrence, with a hazard ratio of 0.03 (95% CI 0-0.26; p < 0.001) and a number needed to treat of 20 to prevent one stroke in 5 years. The REDUCE trial 1 also demonstrated a significant reduction in ischemic stroke with PFO closure, with a hazard ratio of 0.23 (95% CI 0.09-0.62; p = 0.002) and a number needed to treat of 28 to prevent one stroke in 2 years.

Key considerations for PFO closure include:

  • Patient selection: carefully selected patients under 60 years with moderate-to-large shunts and no other identified stroke cause
  • Procedural complications: potential risks include atrial fibrillation, device embolization, and vascular access complications
  • Antiplatelet therapy: dual antiplatelet therapy with aspirin and clopidogrel for 1-6 months, followed by single antiplatelet therapy indefinitely
  • Benefit: reduction in recurrent stroke risk, with relative risk reductions of 40-80%

Overall, the evidence supports PFO closure as a treatment option for selected patients with cryptogenic stroke, and PFO closure should be considered for patients who meet the specified criteria, after careful consideration of the potential benefits and risks 1.

From the Research

Evidence for Patent Foramen Ovale Closure

The evidence for patent foramen ovale (PFO) closure in the setting of cryptogenic stroke is based on several studies that have compared PFO closure with medical therapy.

  • PFO closure has been shown to be superior to medical therapy in preventing recurrent stroke in patients with cryptogenic stroke, particularly in those with atrial septal aneurysm or large shunt 2, 3, 4.
  • A meta-analysis of 6 randomized controlled trials (RCTs) found that PFO closure was associated with a decreased risk of stroke (OR 0.34,95% CI 0.15-0.79, p = 0.012) 3.
  • Another study found that PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (RR = 0.36,95% CI: 0.17-0.79) 4.
  • However, PFO closure may be associated with cardiac complications, including an increased incidence of new atrial fibrillation 2, 3, 4.

Patient Selection for PFO Closure

The selection of patients for PFO closure is crucial, and several factors should be considered, including:

  • The presence of atrial septal aneurysm or large shunt, which may increase the benefit of PFO closure 3, 4.
  • The size of the shunt, with larger shunts deriving more benefit from PFO closure 3.
  • The type of medical therapy used, with antiplatelet therapy or anticoagulation being compared in several studies 5, 4.
  • The age of the patient, with younger patients potentially benefiting more from PFO closure 6.

Medical Therapy for Cryptogenic Stroke with PFO

Medical therapy for cryptogenic stroke with PFO includes antithrombotic agents, such as antiplatelet therapy or anticoagulation.

  • A meta-analysis found that anticoagulation conveyed no net benefit in prevention of recurrent stroke compared with antiplatelet treatment (OR = 0.66,95% CI 0.41-1.07) 5.
  • However, anticoagulation may be beneficial in patients with high RoPE score, which may help in selecting patients benefiting from anticoagulation 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Device closure for patent foramen ovale in patients with cryptogenic stroke: which patients should get it?

European heart journal supplements : journal of the European Society of Cardiology, 2020

Research

Updated meta-analysis of closure of patent foramen ovale versus medical therapy after cryptogenic stroke.

Cardiovascular revascularization medicine : including molecular interventions, 2019

Research

Aspirin or anticoagulation after cryptogenic stroke with patent foramen ovale: systematic review and meta-analysis of randomized controlled trials.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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