Medical Therapy for PFO with TIA When Closure is Denied
For patients with PFO and TIA who cannot undergo closure, either antiplatelet therapy or anticoagulation is recommended, with the choice between them being equivalent based on current evidence. 1
Primary Recommendation
Both antiplatelet therapy and anticoagulation are acceptable options for secondary stroke prevention in PFO-associated TIA when closure is not performed. The Canadian Stroke Best Practice Guidelines (2018) explicitly state that "either antiplatelet or anticoagulant therapy is recommended for secondary stroke prevention" in patients aged 60 years or younger with PFO-attributed stroke/TIA who do not undergo closure. 1
Key Evidence Supporting Equivalence
The PICSS substudy of WARSS found no significant difference in recurrent stroke or death rates between aspirin 325 mg and warfarin (target INR 1.4-2.8) in cryptogenic stroke patients with PFO over 2 years of follow-up. 1
The American Heart Association/American Stroke Association (2006) guidelines state that "antiplatelet therapy is reasonable" (Class IIa, Level B) as the primary recommendation, with warfarin reserved for "high-risk patients who have other indications for oral anticoagulation such as those with an underlying hypercoagulable state or evidence of venous thrombosis" (Class IIa, Level C). 1
Clinical Decision Algorithm
Choose Antiplatelet Therapy (First-Line) When:
- No evidence of deep vein thrombosis or pulmonary embolism 1
- No underlying hypercoagulable state identified 1
- Patient preference favors avoiding anticoagulation monitoring 1
- Lower bleeding risk profile desired 1
Choose Anticoagulation When:
- Evidence of venous thromboembolism (DVT/PE) is present 1
- Documented hypercoagulable state exists 1
- Patient has recurrent events despite antiplatelet therapy 2
- Individual risk-benefit assessment favors anticoagulation 1
Important Caveats
Dual antiplatelet therapy (DAPT) is NOT specifically recommended for PFO-associated stroke/TIA. The guidelines consistently reference single antiplatelet therapy or anticoagulation, not DAPT. 1 DAPT with aspirin and clopidogrel was studied in the ARCH trial for aortic arch atheroma (a different condition), where it showed no significant difference compared to warfarin. 1
Critical Diagnostic Requirements Before Treatment
- Confirm the TIA diagnosis with positive neuroimaging or cortical symptoms 1
- Exclude atrial fibrillation through prolonged cardiac monitoring 3
- Rule out other stroke etiologies including carotid disease, aortic atherothrombosis, and left atrial/ventricular thrombus 3
- Evaluate for underlying hypercoagulable states or venous thrombosis 1
Observational Data Suggesting Anticoagulation Superiority
While guidelines state equivalence, some observational studies suggest warfarin may be more effective:
A Canadian cohort study (1999) found warfarin superior to antiplatelet therapy or no therapy in preventing recurrences in cryptogenic stroke patients with PFO (hazard ratio 2.88 for antiplatelet vs. warfarin, p < 0.04). 2
Another Canadian study (2007) showed a trend toward more strokes in the antiplatelet arm compared to anticoagulation (p = 0.072 for strokes alone, p = 0.012 for composite endpoint). 4
However, these observational findings have not been confirmed in randomized trials, and the PICSS randomized substudy showed no significant difference. 1 The guidelines appropriately prioritize the randomized evidence over observational data.
Practical Implementation
Start with single antiplatelet therapy (aspirin or clopidogrel) unless specific indications for anticoagulation exist. 1 This approach:
- Aligns with the highest quality guideline recommendations 1
- Minimizes bleeding risk in the absence of clear anticoagulation indications 1
- Provides adequate secondary prevention based on randomized trial evidence 1
Switch to anticoagulation if: