New Practice Advisory: Recurrent Stroke in PFO

August 11, 2016
Veronica Hackethal, MD

The American Academy of Neurology has issued a new practice advisory on recurrent stroke in patients with patent foramen ovale.

The American Academy of Neurology (AAN) has issued a new practice advisory on recurrent stroke in patients with patent foramen ovale (PFO). The report was published online in Neurology.

Previous 2004 AAN guidelines had concluded that there was insufficient evidence to establish optimal therapy recommendations for prevention of recurrent stroke in patients with PFO and past cryptogenic stroke. 

To update the guidelines, the AAN’s Guideline Development, Dissemination and Implementation Subcomittee convened a panel of experts to do a systematic literature review of randomized controlled trials (RCTs) evaluating whether percutaneous closure of PFO is better than medical therapy alone, and whether anticoagulation is better than antiplatelet therapy for prevention of recurrent stroke in this population. The literature search identified 809 articles, five of which were deemed relevant for classification. Recommendations were reached by informal consensus.

The evidence review reached the following conclusions:

• Percutaneous PFO closure using the STARFlex device:

♦ Efficacy: No large benefit compared to medical therapy in recurrent stroke prevention (risk difference [RD] 0.13%, 95% confidence interval [CI] -2.2% to 2.0%) (low confidence)

♦ Probable increased risk of serious periprocedural complications (absolute risk 3.2%, 95% CI 1.9 to 5.2%) (moderate confidence)

♦ Possible increased risk of new onset atrial fibrillation (AF) (RD 5%, 95% CI 2% to 8%) (low confidence)

• Percutaneous PFO closure using the AMPLATZER PFO Occluder:

♦ Efficacy: Possible decreased risk of recurrent stroke (RD -1.68%, 95% CI -3.18% to -0.19%) (low confidence)

♦ Possible increased risk for new-onset atrial fibrillation (AF) (RD 1.64%, 95% CI 0.07% to 3.2%) (low confidence)

♦ High likelihood of increasing periprocedural complications, with a risk of 3.4% (95% CI 2.3% to 5%) (high confidence)

• Insufficient evidence to determine the efficacy of anticoagulation vs antiplatelet therapy in preventing recurrent stroke (RD 2%, 95% CI -21% to 25%) (very low confidence)

The report made the following recommendations for the prevention of recurrent stroke in patients with PFO and past cryptogenic stroke:

• Percutaneous PFO closure should not be routinely offered outside of a research setting (Level R).

• In rare circumstances, such as recurrent stroke despite adequate medical therapy and no other identified mechanism, the AMPLATZER PFO Occluder may be offered (upon availability) (Level C).

• If there is no other indication for anticoagulation, clinicians may routinely offer antiplatelet medications in place of anticoagulation (Level C).

• In rare circumstances, such as recurrent stroke while on antiplatelet therapy, clinicians may offer anticoagulation (Level C).

The report pointed out that the STARFlex device is not yet available for clinical use. Though some countries are already using the AMPLATZER PFO Occluder, it is currently under review by the US Food and Drug Administration.

The report also stressed the importance of patient counseling and careful evaluation in order to rule out other causes of recurrent stroke when making treatment decisions.

“Clinicians must counsel patients considering percutaneous PFO closure that having a PFO is common; it occurs in about 1 in 4 people; it is impossible to determine with certainty whether their PFOs caused their strokes or TIAs; the effectiveness of the procedure for reducing stroke risk remains uncertain; and the procedure is associated with relatively uncommon, yet potentially serious, complications (Level A),” the authors wrote.

They also pointed out the high costs of an uncomplicated PFO closure (about $15,000 and up), and concluded that cost-effectiveness and closure efficacy are “equally uncertain.”

“Because of the limitations of the efficacy evidence and the potential for serious adverse events, we judge the risk–benefit tradeoffs of PFO closure by either the STARFlex or AMPLATZER PFO Occluder to be uncertain,” they concluded.

At least three largest randomized controlled trials (RCTs) are comparing PFO closure to medication therapy alone. Ongoing studies are also comparing new anticoagulants, factor Xa inhibitors, and direct thrombin inhibitors with antiplatelet medications in the prevention of recurrent stroke.

Take-home Points

• Updated Practice Advisory from the American Academy of Neurology (AAN) has made the following recommendations for the prevention of recurrent stroke in patients with PFO and past cryptogenic stroke:

♦ Percutaneous PFO closure should not be routinely offered outside of a research setting (Level R).

♦ In rare circumstances, such as recurrent stroke despite adequate medical therapy and no other identified mechanism, the AMPLATZER PFO Occluder may be offered (upon availability) (Level C).

♦ If there is no other indication for anticoagulation, clinicians may routinely offer antiplatelet medications in place of anticoagulation (Level C).

♦ In rare circumstances, such as recurrent stroke while on antiplatelet therapy, clinicians may offer anticoagulation (Level C).

Reference: Messé SR, et al. Practice advisory: recurrent stroke with patent foramen ovale (update of practice parameter): report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2016 Jul 27. [Epub ahead of print]