Antithrombotics After PFO Closure: Much to Discuss, Little Data to Inform

Patent foramen ovale (PFO) closure has become a widely accepted and standardized procedure for preventing recurrent stroke, but what patients should receive in the way of postintervention prescriptions varies widely, experts said during a dedicated session at TVT Connect.

“There is a lot of uncertainty what should be done post-PFO closure in terms of medical therapy, because there’s no good data,” session moderator Jonathan Tobis, MD (University of California, Los Angeles), told TCTMD. “I think cardiologists have extrapolated from their experience with coronary artery stents where we use dual antiplatelet therapy [DAPT] and in some respects it’s not unreasonable—you’ve got a foreign body or device in the arterial system and platelets could adhere to the device. That doesn’t seem to be clinically the case. [It’s] very rare, I would say, thrombus formation on the device.”

The various randomized trials of PFO closure tended to use standard DAPT durations as recommended for coronary stents: RESPECT and CLOSE used DAPT for 1 and 3 months, respectively. But a panel of experts speaking on the issue Wednesday said their practice ranges anywhere from 1 to 6 months, potentially less if a patient reports bruising.

When to Stop Aspirin?

At TVT, Amar Krishnaswamy, MD (Cleveland Clinic, OH), provided a case example of a 37-year-old woman who had a stroke with full clinical resolution whom he treated with PFO closure and discharged on aspirin and clopidogrel. “When she called back a month later with bruising, we discontinued the clopidogrel. She was still bruising at follow-up and said: do I really have to take this aspirin for the rest of my life?” he explained.

“The most recent American Academy of Neurology recommendations . . . in addition to recommending PFO closure in appropriately selected patients also recommends that all patients with a previous stroke should be treated with an antithrombotic regardless of whether a PFO is present or if it's closed,” Krishnaswamy said. “So the question is, first of all, what are the risks of long-term aspirin therapy? What kind of data do we have to guide us in this circumstance, though limited?”

Research has shown that aspirin can reduce the recurrence and severity of stroke up to 12 weeks following ischemic stroke, but “it’s not terribly clear” whether it does much after that point, he said, acknowledging that research is lacking here specifically regarding PFO-associated strokes.

For everybody to take aspirin . . . is not nothing. There is certainly the risk there. Amar Krishnaswamy

David Thaler, MD, PhD (Tufts Medical Center, Boston, MA), who served as a panelist during the session, said he quickly calculated the Risk of Paradoxical Embolism (RoPE) score of Krishnaswamy’s patient to be 9, meaning that her PFO was 88% likely to have caused her stroke. “That means that 12% of patients in this population will have PFO-unassociated stroke,” he said. “The problem is there's going to be a percentage greater than zero of subjects who will have PFO-unassociated stroked and if cardiologists ‘cure’ them with PFO closure and tell them they don't need to have secondary stroke prevention after that, then there's going to be a percentage who are untreated. Clearly the risks of treatment are important, and I think highlighting those is important, but at least in your mind you should be a little bit cautious.”

Krishnaswamy agreed but pointed out that “for everybody to take aspirin . . . is not nothing. There is certainly the risk there,” he said. “Not to say that all patients are fair to discontinue their antiplatelet therapy, but I think patient-specific decision making is appropriate.”

Also, he said, “as interventional cardiologists we put devices into people's hearts and arteries, [and] we worry about endothelialization and thrombogenicity. We know at least in canine models out to about 3 months, there's really nice endothelialization at least of these Gore [Cardioform] devices and so perhaps that is also less of a consideration in that regard.”

Ultimately, Krishnaswamy said, “indefinite aspirin for secondary prevention is certainly recommended by the major societies, and I'm not certainly making a claim that that shouldn't be the case. I think we're still early in these ideas . . . . Aspirin certainly increases the risk of bleeding, we know that to be true. Small analyses have suggested the safety of discontinuing antiplatelet therapy after PFO closure. I think for young patients with no other stroke risk factor, maybe discontinuation of antiplatelet therapy is reasonable. Of course, if the etiologic workup of stroke suggests other reasons to continue antiplatelet therapy—that's important to understand.”

Varying Practice, Lacking Data

Tobis asked about the case patient’s use of estrogen hormonal therapy. “I always wonder about if someone's on birth control pills, they have a stroke, and then they stop their birth control pills, what is the subsequent risk of a next event even if you don't close the PFO, if you remove the stimulus for the thrombogenicity?”

Krishnaswamy said that while she had not been on birth control pills for 2 years prior to her event, even if she had, he would have a hard time only advising her to stop taking them and do nothing else to prevent further strokes. “Just to say, ‘Stop your oral contraceptives. You're going to be okay despite this PFO with an aneurysm and large shunting’? Frankly as patients, I think we all know, they're really uncomfortable with that discussion and that conversation, which I think is completely fair. So even if I think they stop the oral contraceptives in those patients like you describe I still go ahead with PFO closure because I think it's often been the clinically and psychologically appropriate decision.”

Tobis said he closes these PFOs as well but doesn’t think there is enough data to necessarily back-up this practice either way.

“I do as Amar does. I take it as a case by case basis. I don't think it's one size fits all,” said panelist Clifford J. Kavinsky, MD, PhD (Rush University Medical Center, Chicago, IL). “I believe in tailoring the therapy to the patient. A 37-year-old, no risk factors, sure, they can come off antiplatelets. Someone who's closer to 60, maybe has some high blood pressure, yeah, I would continue that.”

Kavinsky, who admitted to “being kind of lax” about discontinuing aspirin, added that he prescribes between 3-6 months of DAPT. “I struggle with this, and this is a really important topic because there's no data to guide us,” he said. “It's just by convention. I think this begs a formalized approach, and I think that you are going to see some guidelines coming out in the next year or two from some societies that are going to try and give us some clarity on this issue.”

“Three to 6 months is longer than was used in the trials,” Thaler pointed out. “I would just point out that the risk of intracranial hemorrhage is probably higher in stroke patients with DAPT than in typical cardiology patients with DAPT, so we have to respect dual antiplatelets a little bit. I use it enthusiastically. I also stop it enthusiastically. Here we do it for a month.”

Tobis also said he uses DAPT for a month, but will stop both antiplatelet agents if the patient reports bruising. Also, if the patient has a history of deep vein thrombosis, he opts for anticoagulation therapy instead.

While it’s possible that some patients might be discontinuing aspirin on their own, Thaler said this would likely depend upon “how dogmatic your neurologist is. I completely take this point about young patients, perhaps it's worth discontinuing it,” he said. “I get it. If we ‘cure’ them [with PFO closure], it makes sense to stop it especially if there's bruising and stuff. But in general, an aspirin a day is relatively harmless. There’s risk of GI bleeds and stuff, but that's different. You have to balance that against risk of stroke, and I generally am pretty aggressive about telling my patients to continue.”

To TCTMD, Tobis said that the wide practice variation here is “probably ok because the complication rate with dual antiplatelet therapy is not that high. There is some bleeding, it’s uncomfortable for the patients if they have subcutaneous bleeding or GI bleeding, but then you stop the medication. I have not seen catastrophic events. . . . So yes, it's a mild problem or a concern, but it doesn’t seem to be a huge problem.”

The field doesn’t need a study looking at the optimal duration of DAPT after PFO closure, he argued, adding that it would be hard to fund anyway. “Maybe you could add that to a study, but that makes it pretty complicated,” Tobis said. However, it might be more appropriate to study postprocedural A-fib by monitoring patients with implantable loop recorders and potentially randomize them to DAPT or single antiplatelet therapy. “A lot of the patients that we put on Plavix, we’re not testing [platelet reactivity], so we don’t even know if the Plavix is working,” he added. “Presumably in some patients you’re just treating with aspirin 81 mg, and again they seem to do well.”

Other talks in Wednesday's session covered the ongoing RELIEF-PFO study for migraine as well as the latest nomenclature change in the field to call stroke in this setting “PFO-related” instead of “cryptogenic.”