PFO Closure After Stroke Shows Long-term Benefits

January 29, 2019

For patients who underwent closure of a patent foramen ovale (PFO) after having experienced a cryptogenic stroke or transient ischemic attack (TIA), the rate of long-term recurrent stroke was low. The finding, from a new observational study, reinforces the benefits of this procedure.

The study, which had an average follow-up of 12 years, also raises the question of whether the long-term use of aspirin is necessary in this population. No strokes occurred in patients who discontinued aspirin, although there were several serious bleeding events, including one death, in those who continued taking aspirin.

"Our results provide a reassuring message on PFO closure after cryptogenic stroke," senior author Josep Rodés-Cabau, MD, Quebec Heart and Lung Institute, Canada, told Medscape Medical News.

He noted that three recent randomized trials have shown substantial benefit, with respect to preventing thromboembolic events, in closing a PFO for patients who have had a stroke for which there was no other suspected cause, but these trials had only limited follow-up.

"These patients are often younger than in normal cardiology — the mean age in our study at baseline was 47 years. It is therefore important to know whether the protective effects of PFO closure remain over the long term, and our data suggest strongly that they do," Rodés-Cabau said.

"We have shown a very low rate of recurrent stroke of about 1% with a median follow-up of 12 years, but some patients were followed out to 17 years," he added. "So our data strongly reinforce the results from the randomized studies."

The current study was published online January 29 in the Journal of the American College of Cardiology.

The study included 201 consecutive patients (mean age, 47 years) from two Canadian hospitals who underwent PFO closure because of a cryptogenic embolism (stroke, 76%; transient ischemic attack, 32%; systemic embolism, 1%).

Echocardiographic examinations were performed at 1- to 6-month follow-up. Data regarding ischemic events, bleeding events, and the use of antithrombotic medications were collected at a median follow-up of 12 years (range, 10 to 17 years); follow-up was complete in 96% of the patients.

Results showed that the PFO closure device was successfully implanted in all cases. Residual shunt was observed in 3.3% of patients on follow-up echocardiography. A total of 13 patients had died at follow-up, all from noncardiovascular causes. Nondisabling stroke occurred in two patients (1%, or 0.08 per 100 patient-years), and TIA occurred in six patients (2.9%, or 0.26 per 100 patient-years).

A history of thrombophilia (present in 15% of patients) tended to be associated with a higher rate of ischemic events at follow-up (P = .067).

Bleeding events occurred in 13 patients. They were major (intracranial bleeding) in four patients (2%; all of these patients were taking aspirin therapy at the time of the event).

A total of 42 patients stopped aspirin treatment at a median of 6 months after PFO closure. None of these patients experienced any ischemic or bleeding episode after a mean of 10 years from treatment cessation.

"The results of this study showing the low stroke rate >10 years post-PFO closure support the long-term efficacy and safety of this treatment for patients with PFO and cryptogenic embolism (stroke, TIA, systemic embolism)," the authors conclude.

"Also, the study suggests that bleeding may exceed ischemic events at long-term follow-up in such patients and points out the possibility of short-term (<12 months) antiplatelet treatment as a safe option to be evaluated in future studies," they add.

Rodés-Cabau pointed out that the randomized studies of PFO closure after cryptogenic stroke were conducted in young patients (younger than 60 years), and the indication for PFO closure after cryptogenic stroke is restricted to that age group. "Having said that, if I had a 63-year-old patient who had had a cryptogenic with no other risk factors but with a PFO, then, yes, I would still close it."

Is Lifelong Aspirin Necessary?

He said the aspirin findings were more controversial. "One fifth of our population stopped taking aspirin in the year following PFO closure, and there were no recurrent strokes in this group," he said. "Aspirin does not come without a price, and the risk of bleeding complications with aspirin is much higher than the risk of ischemic events in this population. In this study, in those who continued on aspirin, there were four intracranial hemorrhages, one of which was fatal.

"There is always a recommendation to take aspirin for life after having had an ischemic stroke, but these patients are a particular population — we believe the stroke was caused by venothromboembolism caused by the PFO. By closing the PFO, we seem to have taken away that risk," Rodés-Cabau suggested.

However, he cautioned that these data were not from a randomized trial, and most of the patients were young and healthy and had no other risk factors. "We can't say anything definite from this observation. It should only be treated as an exploratory analysis, but it is something to think about — the possibility of stopping aspirin in such patients where there are no other risk factors."

Another interesting observation from the study is that in the 22% of patients who experienced migraines before PFO closure, 89% reported an improvement in migraine attacks after the procedure. The improvement was maintained at long-term follow-up.

Also, close to one half of patients who had a history of migraine had migraine with aura, and the majority of them experienced some benefit of PFO closure with respect to migraine attacks, the researchers report.

"However, these data should be interpreted with caution as no details about the specific number and severity of migraine attacks were available in this study," they add.

A "Mechanical Vaccination"

In a very upbeat editorial that accompanied the article, Bernhard Meier, MD, University Hospital, Bern, and Fabian Nietlispach, MD, PhD, University of Zurich, Switzerland, say the study reinforces what was already suspected — that "PFO has a license to kill" and that "PFO closure behaves like a mechanical vaccination."

"PFO closure durably protects against paradoxical embolism causing ischemic cerebral and logically other systemic events, and the price for this in terms of side effects is minimal," they write. "What this report tells that PFO closure is safe and effective, and the effect is durable, not to say permanent."

The study also suggests, for the first time, that with regard to antithrombotic therapy, using just aspirin alone "confers a bothersome risk for bleeds without protecting against anything, once the prime culprit, the PFO, has been taken care of," they note.

They suggest that neurologists will have to rethink the practice of prescribing long-term aspirin in these patents as well referring to a stroke in the presence of a PFO as cryptogenic or an embolic stroke of undetermined cause (ESUS).

The editorialists believe guidelines need to change so that PFO closure is put first in the selection of preventive treatment after ischemic events in otherwise healthy people.

Meier and Nietlispach recommend that the occurrence of a PFO be investigated in all stroke patients and that if a PFO is found, that it be closed. "PFO closure is the easiest, most effective, and probably most cost-efficient way of stroke prevention," they write.

They also suggest that PFO closure could have a role in primary stroke prevention; the prevention of myocardial infaction or peripheral emboli; and improvement of migraine, sleep apnea, platypnea orthodeoxia, exercise desaturation, and enhanced safety in diving and mountaineering.

"For patients with hypercoagulability or planned major surgery, PFO closure as primary prevention makes sense and that may hold true for all high-risk PFOs, that is, those with an atrial septal aneurysm, a Eustachian valve, or a large hole," they add.

Asked whether PFO closure should be investigated for the general population, Rodés-Cabau said this would not be feasible.

PFO is very common, occurring in about 20% of the population, he said. "It would not be practical to close it in all individuals, and studies suggest that in the general population, having a PFO does not confer a major increased risk. But once someone has had a stroke, they do seem to be at higher risk of having another, and this risk is reduced by closing the PFO.

"But otherwise healthy people with a PFO do have a small increased risk of thromboembolism. My advice to people who know they have a PFO is to move around more — especially on long-haul travel. We should all do this to reduce our risk of thromboembolism, but I would say it's probably more important if you know you have a PFO."

Rodés-Cabau holds the Canadian Research Chair "Fondation Famille Jacques Larivière" for the Development of Structural Heart Disease Interventions. The other study authors have disclosed no relevant financial relationships. Meier has received speaker and proctor fees from Abbott. Nietlispach has received speaker and proctor fees from Abbott, Edwards, and Medtronic. Nietlispach has received speaker and proctor fees from Abbott, Edwards, and Medtronic.

J Am Coll Cardiol. Published online January 29, 2019. Abstract, Editorial


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