PFO Closure in Adults Over 60 Safe, but Patient Selection Key

An ideal randomized trial in this space would be in those with high-risk PFO features like ASA and large shuts, says David Kent.

PFO Closure in Adults Over 60 Safe, but Patient Selection Key

Closure may be safe in patients older than 60 years who’ve had a presumed patent foramen ovale (PFO)-related stroke—a population excluded from most of the randomized trials in this space—but may also be linked to a greater likelihood of recurrent cerebrovascular events compared with when it’s done in younger patients, according to new observational data.

Prior research has shown that there is a relationship between older age and risk of recurrent stroke in patients with PFOs. As PFO closure has become routine practice for secondary prevention of cryptogenic stroke in the under-60 cohort, many over that cutoff are still being evaluated for the procedure with minimal data in support of it.

“More and more, we receive patients from neurologists and internal medicine specialists that are older than 60—could be 65, could be 70, sometimes even older,” senior author Josep Rodés-Cabau, MD, PhD (Quebec Heart & Lung Institute/Laval University, Canada), told TCTMD. “We assume that the results will be similar, but we don't have strong evidence yet. . . . We are doing this a bit off label. We are translating the results of the young patients to older patients, and we wanted to see whether the results were similar or not.”

Event Rate Lower Than Expected

For the study, published online last week in Circulation: Cardiovascular Interventions, Rodés-Cabau, lead author Alberto Alperi, MD, PhD (Quebec Heart & Lung Institute/Laval University, Canada), and colleagues included 388 and 883 patients who had previously undergone PFO closure when aged over 60 (mean 67 years) and no more than 60 (mean 44 years), respectively.

Older patients had a greater degree of vascular complications like diabetes and hypertension, and were also more likely to have prior atrial fibrillation (AF), CAD, pulmonary embolism, and deep vein thrombosis as well as atrial septal aneurysm (ASA). Average Risk of Recurrent Paradoxical Embolism (RoPE) score—the score used to estimate the probability that a documented PFO is causally related to stroke—was also significantly lower in patients older than 60 (4.6 vs 7.2; P = 0.001). Overall procedural success was high (99.9%), and procedural complications were low (< 2%).

Over 3 years of follow-up, the older cohort showed a lower-than-expected rate of the combined endpoint of stroke, TIA, and peripheral embolism compared with what was predicted by their average RoPE score (1.61 events per 100 patient-years; O-to-E ratio 0.31; 95% CI 0.11-0.91).

Even so, the rate of recurrent cerebrovascular events was higher in the older compared with the younger patients over time (incidence rate ratio 4.7; 95% CI 2.36-9.8). New-onset AF was especially higher in the older population (2.66 vs 0.49 per 100 patient years; P < 0.001).

What Happens With Age?

The reason why older patients might not benefit from PFO closure, and why they were excluded from most of the original trials, is because with older age comes an increased likelihood that cryptogenic strokes being caused by sources other than a PFO, including paroxysmal AF and subclinical atheroma.

“The reason why their recurring risk was higher is because these are higher-risk mechanisms than paradoxical embolism,” David Kent, MD (Tufts Medical Center/Tufts University School of Medicine, Boston, MA), who was not involved in the study, told TCTMD. “For paradoxical embolism, the recurrence risk is less than 1% per year. But it's higher for other mechanisms, and in older patients these other mechanisms become progressively more common.”

Even so, he said the results of this study are not unexpected. “This shows that we need a trial, and the question for the trial is really not: does this work for anybody over 60? I think we know that it does work for some patients over 60,” Kent commented. “The question for the trial is: how do we select those patients in whom it's likely to work?”

Kent would like to see a trial randomize patients in their 60s who have a PFO with a high-risk feature, like a large shunt or ASA, to closure or optimal medical therapy.

“Absent a trial, it's not unreasonable to consider closing these patients,” he said. “But it's also not unreasonable to treat them medically. The margin of benefit in the patients on the absolute scale is going to be relatively small, almost certainly no greater than a couple of percentage points in terms of stroke recurrence over a 5-year time horizon. So we really need a randomized trial to assess the balance of the benefits and harms.”

Rodés-Cabau, too, argued there is a need for randomized trials in older patients. Until those come, the way he will assess older patients for PFO closure is with “an extensive evaluation of the potential causes [with] extended continuous ECG monitoring” in order to exclude AF as the cause. “We have to be more careful in the evaluation of other potential causes because the number of potential causes increases in this population with respect to the younger patients, and you have to be more careful not to miss anything,” he explained.

“The thing is that there is a huge variability depending on the neurology and internal medicine departments of how these patients are evaluated,” he continued, noting that cardiologists may not even be assessing some of these patients if they are never referred. The key to them doing well with PFO closure, ultimately, is good patient selection, Rodés-Cabau said.

He also wanted to highlight the safety of PFO closure overall. “This is an extremely safe procedure,” Rodés-Cabau said. “There was some controversy in prior studies in older patients, but honestly here, we were successful in 99.9% and the complication rate was extremely low, as in younger patients. This is very reassuring. . . . What we showed is that, honestly, the complication rate is so low that it's nothing that should prevent you from sending the patient for a PFO closure.”

  • Alperi reports receiving a research grant from the Martin Escudero Foundation.
  • Rodés-Cabau reports receiving institutional research grants from Abbott Vascular.
  • Kent reports receiving a research grant from Gore.