Experts Give Strong Support for PFO Closure in New ‘Rapid Recommendations’

Beating the major professional societies to the punch, a group of experts has released new “rapid recommendations” that reflect recent data showing that closure of patent foramen ovale (PFO) is beneficial in select patients with cryptogenic stroke.

The new guidance, which applies to patients younger than 60 who have had a cryptogenic ischemic stroke and a comprehensive workup excluding other causes of stroke, gives a strong recommendation for PFO closure plus antiplatelet therapy over antiplatelet therapy alone in patients for whom anticoagulation is not an option.

When all options are on the table, there is a weak recommendation for PFO closure plus antiplatelet therapy over anticoagulation. And when PFO closure is contraindicated, unacceptable, or unavailable, there is a weak recommendation for anticoagulation over antiplatelet therapy.

Neurologist Steven Messé, MD (University of Pennsylvania, Philadelphia), who was not involved in crafting the new document, commented to TCTMD: “From a methodological point of view it seems solid, and I think the recommendations seem reasonable.”

The rapid recommendations, published online July 25, 2018, ahead of print in the BMJ by lead author Ton Kuijpers, PhD (Dutch College of General Practitioners, Utrecht, the Netherlands), and colleagues, are a product of a collaboration between the journal and MAGIC, a nonprofit organization involved in developing and disseminating clinical practice guidelines and related evidence summaries and decision aids. The idea is to incorporate important trial findings into clinical practice more quickly than can be done through the standard guideline process employed by major medical societies and also to incorporate patient perspectives. The guideline panel, chaired by Frederick Spencer, MD (McMaster University, Hamilton, Canada), included general internists, interventional and noninterventional cardiologists, stroke physicians, epidemiologists, methodologists, statisticians, and people with personal experience with cryptogenic stroke and PFO.

Most guidelines continue to recommend against routine PFO closure in patients with cryptogenic stroke because trial data had been inconclusive. That has changed in recent years, however, with trials coming out with data to show that PFO closure reduces the risk of ischemic stroke compared with other approaches.

The rapid recommendations were made on the basis of a systematic review sparked by results from three randomized controlled trials—long-term data from RESPECT and principal findings from CLOSE and REDUCE—published in September 2017.

Pooling the results together, there is evidence that PFO closure plus antiplatelet therapy probably results in a large decrease in ischemic stroke compared with antiplatelets alone, with little to no impact on death, major bleeding, pulmonary embolism, TIA, or systemic embolism, according to Kuijpers et al. When compared with anticoagulants, the impact of closure on ischemic stroke is lower, although it probably decreases major bleeding, they conclude. Those benefits come at the cost of increases in persistent A-fib and device- or procedure-related adverse events.

The weak recommendation for PFO closure over anticoagulation “reflects (in addition to the low certainty in the estimates of effect) that most serious complications of PFO closure are usually short-term, whereas anticoagulation imposes a long-term burden and increased risk of major bleeding,” the authors explain. “Most fully informed patients would probably accept the transient risk of major adverse events rather than the long-term bleeding risk, but a substantial minority would probably choose anticoagulation.”

When considering anticoagulants or antiplatelets in patients for whom PFO closure is not an option, both should be discussed with patients, the authors say, noting that anticoagulation may decrease ischemic stroke but increase major bleeding. “The panel felt that the possible decrease in ischemic stroke with anticoagulants would be more important to most patients than the probable increase in major bleeding,” they say. “We expect variability in how patients might value these outcomes. Shared decision-making may help establish what matters most to each patient.”

Time to Change Guidelines

Though major guidelines issued before the recent positive trials were reported continue to recommend against routine PFO closure, that will likely change in the near future.

Messé, who headed the American Academy of Neurology (AAN)’s recommendations against routine closure, said it is time to revisit the guidance considering the latest data. Indeed, he said, an update is currently in draft form.

“The new evidence that’s available is supportive of PFO closure,” he told TCTMD. “The AAN document is not finalized and I can’t really speak to what it will finally look like, but I think in some form it will probably recommend closure in select patients.”

The question then becomes how to pick the patients most likely to benefit from PFO closure. “I definitely think that’s the crux of the issue, and I think that the best bet for clinicians in practice is to try to recapitulate what was done in the studies that were positive,” Messé said. More specifically, that means carefully ruling out causes of stroke other than the PFO.

It appears that practice has already started changing even as guidelines have been slow to catch up to the new data.

“For myself, if I see a young patient with a stroke and a thorough workup only reveals a PFO, then I’m going to be inclined to recommend they consider PFO closure,” Messé said, stressing, however, that it’s important for cardiologists and neurologists to work together to determine the final course of action.

Some Concerns

Messé said his perspective on PFO closure has changed in the face of the new data supporting its use, but he still expressed some concerns about how the procedure could be employed out in the community. PFO is a common finding, affecting about 25% of the general adult population, and some—if not most—PFOs found in patients with cryptogenic stroke will be innocent bystanders, he explained.

“I think it’s important that we apply that data appropriately, but I do worry that out in the real world that people are going to take this as a green light to close every PFO they come across,” Messé said. “I hope that doesn’t happen, but we’ll see.”

Shunichi Homma, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), a cardiologist who is involved in the AAN guidelines, also cited some concerns about going too far with expanding use of PFO closure. In particular, PFO closure devices carry a not insignificant rate of complications, and that’s at experienced centers. Spreading the procedure to additional centers could bump those rates up even more, “which worries me,” Homma said, noting that complications might be underreported.

Still, he said, recent data do support offering PFO closure to additional patients, as long as they have a cryptogenic stroke by strict definitions and their preference is for closure over either antiplatelets or anticoagulants.