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Clinical Question

PFO closure for cryptogenic stroke?

Synthesises 7 trialsFrom the early trials that missed their primary endpoint (CLOSURE-I, PC, RESPECT 2013) to the positive 2017 cluster and DEFENSE-PFO; AF excess is the trade-off

Clinical Synthesis

Whether PFO closure helps depends far less on the presence of a PFO than on how likely that PFO caused the stroke: pooled trial data show a roughly 60% relative reduction in recurrent stroke on average (adjusted HR 0.41), but the benefit concentrates in patients whose PFO is the probable culprit, and the atrial fibrillation excess falls hardest on the patients in whom it is not.

Bottom line

Select on causal likelihood, not on the mere presence of a PFO. In patients 18 to 60 with nonlacunar cryptogenic stroke, a PFO, and no competing etiology after vessel imaging, prolonged cardiac monitoring, and echocardiography with bubble study, closure plus long-term antiplatelet is reasonable as a decision made jointly with cardiology and the patient (Class IIa, Level B-R), and the case is strongest when the RoPE score is high or the PFO carries high-risk anatomy. When causal likelihood is low, expect no stroke reduction and a larger atrial fibrillation excess: that is the group to leave alone.

Sources

§5.2.2 Patent Foramen Ovale· 2021Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke· 2021Patent Foramen Ovale Closure in Stroke and the PASCAL Classification System· 2026Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale (CLOSURE I)· 2012Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Embolism (PC Trial)· 2013Closure of Patent Foramen Ovale versus Medical Therapy after Cryptogenic Stroke (RESPECT· 2013Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke· 2017Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke· 2017Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke· 2017Cryptogenic Stroke and High-Risk Patent Foramen Ovale· 2018Patent Foramen Ovale Closure Decreases the Incidence but Not the Size of New Brain Infarction on Magnetic Resonance Imaging· 2021Twenty-Year Follow-Up After Patent Foramen Ovale Closure in Patients With Paradoxical Embolism· 2026Risk of Ischemic Stroke After Patent Foramen Ovale Closure· 2024Transcatheter Closure of Patent Foramen Ovale With a Novel Biodegradable Device· 2026Patent Foramen Ovale and Stroke· 2025

Trials in this question· 7

CLOSURE I2012
First major PFO closure RCT; STARFlex device did not reduce stroke/TIA recurrence vs medical therapy. Negative.
Primary not metHR 0.78 (0.45–1.35), P=0.37
PC Trial2013
Second major PFO closure RCT; Amplatzer device did not reduce composite events vs medical therapy. Underpowered; negative primary.
Primary not metHR 0.63 (0.24–1.62), P=0.34
RESPECT (Original 2013)2013
Original 2013 RESPECT primary publication; ITT primary NOT met at median 2.1y (HR 0.49, P=0.08 borderline). The 2017 extended follow-up later converted the result.
ITT P=0.08HR 0.49 (0.22–1.11)
CLOSE2017
In cryptogenic stroke <60 with PFO + ASA or large shunt, PFO closure abolished recurrent stroke vs antiplatelet alone.
NNT 20HR 0.03 (0.00–0.26)
REDUCE2017
In cryptogenic stroke 18–59 with PFO and clean antiplatelet comparator, Gore HELEX/Cardioform closure beat antiplatelet alone on clinical stroke.
NNT 28HR 0.23 (0.09–0.62)
RESPECT (long-term)2017
In cryptogenic stroke 18–60 with PFO, Amplatzer Occluder beat medical therapy on recurrent stroke over a median 5.9-year follow-up.
NNT 42 (exploratory)HR 0.55 (0.31–0.999)
DEFENSE-PFO2018
In cryptogenic stroke with HIGH-RISK PFO anatomy (ASA, hypermobility ≥10 mm, or PFO size ≥2 mm), closure markedly reduced 2-year stroke / vascular death / major bleeding vs medical therapy.
NNT 8 over 2y (6 events)0% vs 12.9% at 2y (P=0.013)

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