PFO Closure Guidelines Address Older Adults, Trial-Excluded Groups

ATLANTA -- Scenarios for patent foramen ovale (PFO) closure not covered by the pivotal trials were a key subject of guidelines released by the Society for Cardiovascular Angiography and Interventions (SCAI).

"This document represents the first truly rigorous guideline document put forth by the SCAI to lend clarity to a field surrounded by controversy and aid in physician decision making for PFO associated conditions," guideline writing committee chair Clifford J. Kavinsky, MD, PhD, of Rush University Medical Center in Chicago, said in a statement.

The document, published in the Journal of the Society for Cardiovascular Angiography & Interventions in conjunction with release at the Society's annual meeting here, was also endorsed by the American Academy of Neurology (AAN).

"The FDA labeling has mandated alignment of cardiology and neurology multi-disciplinary team members in patient selection for PFO closure as well as the task of excluding all other potential causes of stroke," the guideline noted.

Its recommendations lined up with the AAN's 2020 practice advisory on PFO and European guidelines as they pertain to populations studied in the pivotal trials, Kavinsky told MedPage Today.

AAN had given a "moderate" level recommendation to PFO closure as "probably" reducing recurrent stroke risk in select patients younger than 60 years with prior stroke that appeared embolic and suggested either antiplatelet or anticoagulation for those who opt for medical treatment alone.

SCAI's document, though, homed in other other populations for which there is even less evidence.

"There has been interest in the benefits of PFO device closure in subsets of patients who were not included in the large RCTs [randomized controlled trials]," Kavinsky's group wrote. "These include patients who are advanced in age or have certain comorbid conditions such as platypnea-orthodeoxia syndrome, diving decompression illness, thrombophilia, systemic embolism, venous thromboembolism (VTE) and patients with PFO and refractory migraine headaches. Although lacking in RCT data, there are data from observational studies to inform guideline recommendations with respect to these patient subsets."

These groups that don't fall strictly within the RCT inclusion criteria, though, are patients who clinicians see every day, so the guidelines will be "extremely" useful, Kavinsky predicted.

The strength of the evidence was moderate for the panel's recommendations for younger and middle-aged patients but low or very low for most other groups.

For adults without a prior PFO-associated stroke: The guidelines recommended against the routine use of PFO closure for the treatment of migraine, for SCUBA divers with prior decompression illness, for thrombophilia, for atrial septal aneurysm, for prior transient ischemic attack, and for history of deep vein thrombosis.

PFO closure was recommended in systemic embolism without other embolic etiologies and in platypnea-orthodeoxia syndrome without other known causes of hypoxia.

For adults with a prior PFO-associated stroke: The guidelines recommended PFO closure rather than antiplatelet medication alone for patients ages 18 to 60 (independent of anatomy) and for those over 60 as well, based on "indirect, very uncertain evidence." It was also recommended for patients with thrombophilia on antiplatelet therapy who are not anticoagulated but not for patients with a history of atrial fibrillation who have had an ischemic stroke.

The SCAI guideline panel suggested PFO closure plus antiplatelet therapy rather than anticoagulation therapy alone in adults, whether over or under age 60, if they have no other indication for anticoagulation.

For patients on anticoagulation after a prior PFO-related stroke, PFO closure was suggested in addition to lifelong anticoagulation for those with thrombophilia or a history of deep vein thrombosis or pulmonary embolism.

The rationale for preferring closure over anticoagulation alone, although controversial, is because patients often have interruption of anticoagulation due to nonadherence, need for surgical procedures, and many other reasons -- "because of the uncertainty of uninterrupted anticoagulation," Kavinsky said.

For all the recommendations, Kavinsky's group wrote, "The decision to perform PFO closure on any patient for any clinical scenario should be highly individualized and nuanced in the context of a mandatory multi-disciplinary team of primary stakeholders which, most importantly, should include the patient and neurologist."

Another stakeholder group that Kavinsky noted might be influenced by the guidelines was third-party payers, who have largely dictated practice patterns.

"Once you drift outside the strict labeling of the FDA, which closely parallels what the inclusion criteria were for the randomized clinical trials, then oftentimes third-party payers don't pay so therefore many patients don't get treated," he said. "I think this guideline will help third-party payers to provide some liberalization of the procedure."

No recommendation was issued for PFO closure at a prolonged time after the stroke in either scenario, with or without a prior PFO-related stroke. Nor was there any recommendation for what antithrombotic regimen to take beyond 1 month of dual antiplatelet therapy after PFO closure.

SCAI recommended against extrapolating the guideline to patients under age 18.

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