PFO Closure for Stroke Is Safe, Effective at 5 Years: REDUCE

Five-year results from the randomized REDUCE trial show a continued benefit of patent foramen ovale (PFO) closure compared with antiplatelet therapy alone for the prevention of cryptogenic stroke.

“Most importantly, this supports the idea that PFO closure in appropriately selected patients has a durable effect with longer-term safety,” lead author Scott Kasner, MD (University of Pennsylvania, Philadelphia), told TCTMD. “Of the prior studies, only one had long-term data. That was the RESPECT PFO trial. The others were all of similar length to the original Gore results [from REDUCE], so it's helpful to know that we have good safety and efficacy data that go out for a longer period of time for more than one device now.”

Those original REDUCE results, presented at the 2017 European Stroke Organisation Conference, showed a relative risk reduction for recurrent ischemic stroke of 77% for PFO closure with the Gore Helex Septal Occluder or the Gore Cardioform Septal Occluder (both WL Gore & Associates) over antiplatelet therapy alone at 3.2 years.

Now, long-term results, published as a research letter in the March 11, 2021, issue of the New England Journal of Medicine, show the intervention maintaining an advantage through a median follow-up of 5 years in preventing recurrent stroke (1.8% vs 5.4%; HR 0.31; 95% CI 0.13-0.76). The two additional strokes reported in the PFO-closure group over the extended follow-up period bring the absolute difference in risk between the cohorts to 3.6% favoring intervention with a number needed to treat of 25 to prevent a single stroke.

Additionally, the rates of serious adverse events, death, major bleeding, and deep vein thrombosis were similar between the study arms. There were no device-related complications in the intervention group over the additional follow-up. Atrial fibrillation (AF) or flutter, however, was increased among those who underwent PFO closure compared with those who did not (6.8% vs 0.4%). This complication lasted more than 30 days in 12 PFO closure patients, one of whom had a recurrent stroke while on anticoagulation.

“Predictors of atrial fibrillation or flutter related to PFO closure and subsequent stroke risk require further investigation, and a patient-level meta-analysis relating to these predictors is underway,” the researchers write.

Kasner said there is much “angst” about AF following PFO closure, because it wouldn’t make sense to trade something that carries relatively low long-term risk of stroke for another condition that carries a higher risk. Questions still remain regarding who is most likely to develop atrial fibrillation after PFO closure and how high the associated stroke risk is, he continued, but it seems to be “good news” that this complication does not seem to be accumulating substantially over time.

REDUCE investigators are currently collaborating with those from RESPECT, CLOSE, CLOSURE I, PF, and DEFENSE PFO to produce an individual patient-level meta-analysis “where we can combine all of the raw data and try to look at things like predictors of atrial fibrillation, predictors of late stroke, other complicating factors,” Kasner said, adding that he expects the results to be released within a year. “This is one step toward that more global harmonization of all of the data.”

The research bubble around PFO closure and stroke has popped with the procedure being approved for this indication for several years now, according to Kasner. “I guess a lot of the world feels like we've now answered the question and we're done, but I think there are still a lot of open questions,” he said. “We don't really know with any certainty if we should be doing this in patients who are over 60 or patients who present only with TIA. . . . We probably have been overly restrictive, but there are a lot of questions still to answer. It just gets harder to answer them when the cat is at least partially out of the bag.”

Additionally, Kasner said the long-term safety findings of this study could have implications for PFO closure for other indications. “The world is getting more experience with these devices for stroke, so if they were pretty safe in the first place and that safety is likely to improve with experience, then maybe that could change the balance for other things that have been associated with PFO, like migraine,” he said.