Age Cutoffs for PFO Closure Deserve a Rethink, Researchers Urge

Current age-based restrictions on patent foramen ovale (PFO) closure should be reconsidered in light of observational data suggesting that carefully selected older patients fare as well as those who are younger despite the presence of more risk factors, newly published research suggests.

In a study of more than 700 patients of varying ages, researchers found no differences in the risk of recurrent cerebrovascular events or complications between older patients, including some well into their 80s, and those younger than age 60.

“In a way, the [US Food and Drug Administration’s] age-based restriction prevents certain older patients from accessing a beneficial procedure. So, while age certainly should inform the preprocedural evaluation, it should not be the sole determinant for guiding the intervention,” lead investigator Eyal Ben-Assa, MD (Assuta Ashdod University Hospital, Israel), told TCTMD.

Pivotal RCTs influential in the full FDA approval of transcatheter-based PFO closure in 2018 largely excluded patients over age 60, and while older patients only account for about 10-15% of those presenting to PFO clinics, data are accumulating to suggest that their risk of procedure-related stroke is real, said Ben-Assa.

“I can understand why the [early] studies didn't include patients above 60 because they have other reasons for strokes. They have more atrial fibrillation and they have more vascular disease,” Ben-Assa told TCTMD. “You need to be very meticulous in the evaluation of those patients to say that the stroke is related to the PFO.”

Data suggest that PFO closure is being performed off-label in some older patients despite the lack of randomized evidence to support the practice. In a recent meta-analysis of Medicare fee-for-service beneficiaries older than 60 who had had an ischemic stroke, clinical outcomes were improved with PFO closure, with a 38% lower risk of recurrent ischemic stroke through 3 years.

While age certainly should inform the preprocedural evaluation, it should not be the sole determinant for guiding the intervention. Eyal Ben-Assa

Commenting for TCTMD, Hemal Gada, MD (University of Pittsburgh Medical Center Heart and Vascular Institute, Harrisburg, PA), said while new data on the issue are welcome, they’re unlikely to move the needle much from a regulatory perspective.

“We need to be all-inclusive as far as age is concerned, and then we have to dissect the data based on the confounding clinical variables that these people come in with and their variable event rates as they age,” he said. “Instead of the restrictions of the clinical trials that were used to supply this therapy to a certain group of the population, we really should be looking at it on a case-by-case basis. I think the real message from this is that we really need to get a little bit more nuanced with how we characterize a high-risk PFO.”

While age may be a part of the equation characterizing risk, Gada said his takeaway from the new study is to “focus more on anatomical features in deciding whether or not someone's going to benefit from PFO closure.”

The study was published October 14, 2024, in JACC: Cardiovascular Interventions.

No Differences in Stroke or TIA Rates

Ben-Assa and colleagues examined data on 741 patients (mean age 68 years) who underwent transcatheter PFO closure following a confirmed PFO-related stroke at a single center prior to 2018. The risk of paradoxical embolism (RoPE) score was used to assess the relationship of PFO to stroke.

Compared with younger patients, those older than 60 (n = 184) were more likely to have hypertension, diabetes, and be smokers. Patients with CV risk factors and those over age 50 had at least 2 weeks of electrocardiographic monitoring prior to the procedure to rule out atrial fibrillation (AF). Device implantation was successful in 99% of the cohort, with similar rates of procedural success and complications between the younger and older patient groups.

The rate of recurrent stroke or TIA was 4.3% at a median of 3.6 years in the older age group and 2.3% in the younger age group (P = 0.20).

Not surprisingly, the rate of all-cause mortality over the follow-up period was higher in the older age group at 5.4% versus 1.4% in younger patients (P = 0.002). There also was a higher likelihood of developing AF in older versus younger patients (7.6% vs 2.7%; P = 0.007).

In survival analyses, recurrent ischemic neurologic events were not different by age (log-rank P = 0.31) and neither were the composite of ischemic neurologic events, reintervention, or neurologic death (log-rank P = 0.52).

“We do think that monitoring for at least 2 weeks or longer with electrocardiographic monitoring such as an implantable loop recorder is important in [those over age 60] to rule out atrial fibrillation,” Ben-Assa said. There also should be thorough assessment for carotid disease and other comorbidities that could be directly responsible for stroke, he added.

Who Benefits and How to Decide?

According to Gada, while age does present a problem, the safety and success of PFO closure in older patients isn’t the primary question that still needs to be answered, which is why he doesn’t think studies like this one are convincing from a clinical and regulatory perspective.

“Patients even over the age of 60 are going to get a safe, predictable outcome with regards to the technical aspects of PFO closure. Whether or not that relates to the effectiveness of the therapy is the question that we should really lean forward and answer,” he said.

We need to be all-inclusive as far as age is concerned. Hamal Gada

Ben-Assa and colleagues, as well as Gada, say that the introduction of the PFO-associated stroke causal likelihood score (PASCAL) is changing discussions around individualized clinical decision-making in this area.

“If we use the nuance of the PASCAL score and maybe even come away from some of those clinical characteristics and redefine a score where the anatomic features are given a little bit more substance in what they can do [as far as prediction], then I think that we're really doing better by our patients,” Gada said. “Regulatory bodies do need to take a look at the role that anatomic issues like atrial septal aneurysm and large shunts play in this specific population, and maybe get into some class of recommendation that uses those two things to foster at least a conversation in your older patient versus just saying, ‘Don't do it. It's harmful,’ because I don't think that that data is there.”