The patient is already on apixaban (Eliquis); could the stroke still be classified as cryptogenic if the possible cause is a patent foramen ovale (PFO) or atrial fibrillation (AF)?

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Last updated: September 6, 2026 • View editorial policy

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Can a Stroke Still Be Classified as Cryptogenic if PFO or Atrial Fibrillation Are Present?

No, if atrial fibrillation has been identified, the stroke cannot be labeled cryptogenic—it becomes a cardioembolic stroke with a known cause. However, if only a PFO is found after extensive workup excludes other causes (including AF), the stroke can still be classified as cryptogenic or more specifically as "PFO-associated cryptogenic stroke."

Understanding the Classification

When AF Is Present

  • Atrial fibrillation is a definitive stroke mechanism that disqualifies cryptogenic classification 1
  • The diagnosis of cryptogenic stroke requires ruling out AF through prolonged rhythm monitoring 2
  • If your patient has documented AF (even paroxysmal), this is the presumed stroke mechanism, and anticoagulation with apixaban is the appropriate treatment 3

When Only PFO Is Present

  • A stroke can remain "cryptogenic" even with a PFO present because approximately 25% of the general population has a PFO 4
  • The key question becomes: Is the PFO causally related to the stroke or merely incidental? 2
  • Clinicians reach cryptogenic stroke diagnosis by systematically excluding:
    • Atrial fibrillation (via prolonged monitoring)
    • Aortic atherothrombosis or left atrial clot (via transesophageal echo)
    • Significant cerebrovascular disease (via imaging) 2

Determining PFO Causality

Use the PASCAL classification system to determine if the PFO likely caused the stroke 4, 5:

PASCAL Classification Combines:

  1. RoPE Score (Risk of Paradoxical Embolism):

    • Incorporates: age, stroke/TIA history, diabetes, hypertension, smoking, cortical infarct on imaging 4
    • Score <3: PFO prevalence similar to general population (23%)
    • Score 9-10: PFO prevalence 77% 4

  2. High-Risk Anatomical Features:

    • Large right-to-left shunt
    • Atrial septal aneurysm 4, 5

PASCAL Categories:

  • "Probable" PFO-related: Younger patients without vascular risk factors + high-risk PFO features
  • "Possible" PFO-related: Intermediate characteristics
  • "Unlikely" PFO-related: Older patients with vascular risk factors, no high-risk PFO features 4

Critical Clinical Pitfall

Your patient is already on apixaban—this suggests AF was detected. If AF has been documented:

  • The stroke is NOT cryptogenic
  • It is a cardioembolic stroke due to AF
  • Continuing apixaban is appropriate 3
  • PFO closure is not indicated when AF is the stroke mechanism 1

If AF Was Never Actually Documented

If apixaban was started empirically without documented AF, you need to:

  1. Verify AF presence through:

    • Review of telemetry/Holter monitoring
    • Consider extended cardiac monitoring if not done 1

  2. If no AF is found:

    • The stroke may be reclassified as cryptogenic
    • Assess PFO causality using PASCAL classification 4, 5
    • Consider PFO closure if patient is 18-60 years old with "probable" PASCAL classification 2, 5

  3. If AF is confirmed:

    • Continue anticoagulation
    • PFO is incidental, not the treatment target 1

Treatment Implications Based on Actual Diagnosis

If Stroke Is Due to AF (Not Cryptogenic):

  • Continue apixaban at standard dosing for stroke prevention in AF 3
  • PFO closure is not beneficial 1

If Stroke Is PFO-Associated Cryptogenic (No AF):

  • For PASCAL "probable" patients <60 years: Strong recommendation for PFO closure plus antiplatelet therapy over antiplatelet alone 2, 5
  • Anticoagulation is NOT recommended for PFO-associated cryptogenic stroke unless there's another indication 5
  • If your patient is on apixaban without documented AF, consider switching to antiplatelet therapy after PFO closure or if closure is declined 2

Bottom Line

The presence of documented AF means the stroke is NOT cryptogenic—it's cardioembolic, and apixaban is the correct treatment. A PFO alone (without AF) can coexist with cryptogenic stroke classification, but determining whether the PFO caused the stroke requires systematic evaluation using the PASCAL classification system 4, 5. You must clarify whether AF was actually documented to determine the appropriate classification and ongoing management.

References

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