Further Calls to Update Guidelines for PFO Closure in Stroke Prevention

Two new meta-analyses mean that now three studies have drawn the same conclusion on the benefits of PFO closure within the past month.

Further Calls to Update Guidelines for PFO Closure in Stroke Prevention

Two more meta-analyses have concluded that a change in guidelines is warranted for the management of cryptogenic stroke, giving percutaneous patent foramen ovale (PFO) closure a more prominent role.

Following the release of a similar report last month, the two studies published online today in the Annals of Internal Medicine—one from Europe and one from the United States—bring to three the number of independent analyses suggesting that PFO closure is more effective than optimal medical therapy alone at reducing the risk of recurrent stroke in select patients.

“Until now, the lack of strong evidence [for a] beneficial effect of PFO closure limited this strategy in daily practice,” said senior author of the European study, Ciro Indolfi, MD (Magna Graecia University, Catanzaro, Italy), in an email to TCTMD. “Now we have the scientific evidence that PFO closure is better than medical therapy in patients with cryptogenic stroke.”

Both Indolfi’s study, led by Salvatore De Rosa, MD, PhD (Magna Graecia University), as well as the one led by Rahman Shah, MD (University of Tennessee, Memphis), included the four randomized controlled trials of PFO closure and medical therapy involving a range of closure devices currently being investigated or commercialized: RESPECT , REDUCE, CLOSE, and PC . Of note, both meta-analyses excluded CLOSURE I, given that the device used in that study is no longer being manufactured.

The findings by De Rosa et al and Shah et al conclude that PFO closure was significantly associated with 3.1% and 3.2% lower risks of recurrent stroke, respectively. However, the risk of new-onset A-fib was increased by 3.3% with PFO closure in the De Rosa paper, an observation also made in the analysis published last month. The Shah study also observed a trend toward higher rates of new-onset A-fib in those treated with PFO closure, but determined that a pooled analysis of this outcome would be “inappropriate” given the between-trial heterogeneity. Additionally, the De Rosa study found that PFO closure was more effective at preventing stroke in patients with larger interarterial shunts (P = 0.034).

Planning Ahead

Given that original results from the PC, RESPECT, and CLOSURE I trials failed to show a benefit of PFO closure over optimal medical therapy due to “small sample sizes and other multifactorial factors,” Indolfi told TCTMD that “many clinicians and interventionalists will be interested to see the combined data on PFO closure.”

Moreover, the European researchers say they “believe that the new evidence warrants a revision of current practice guidelines,” with Indolfi adding that these two studies will be the “conceptual scientific framework” for that change. Current US societal guidelines give PFO closure a class III indication.

In addition, De Rosa and colleagues propose, “this finding of efficacy of PFO closure for patients with cryptogenic stroke might ignite further discussion regarding extending this treatment to primary prevention.”

What will be vital to the success of PFO closure going forward, they add, is “the identification of an efficient tool to stratify stroke risk.” All cases should involve a “comprehensive clinical assessment” to rule out potential causes of stroke and “the ideal work-up should be adapted to the clinical profile of individual patients,” they add. Options include brain imaging, transesophageal echocardiography, prolonged monitoring, vascular imaging, and screening for a hypercoagulable state. After that, patient stroke risk should be further identified using the Risk of Paradoxical Embolism score.

Looking ahead, both papers mention the ongoing DEFENSE-PFO and PFO-PAS studies as well as research on new devices like the FlatStent occluder (Coherex Medical, Salt Lake City, UT), bioabsorbable PFO occluders, and the NobleStitch EL system (HeartStitch, Fountain Valley, CA) that will inevitably affect future practice.

“In patients with PFO and cryptogenic stroke, transcatheter device closure of PFO decreases the risk for recurrent stroke,” Shah and colleagues conclude. “Because rates of recurrent stroke are low even with medical therapy, patients and clinicians should share the decision about PFO closure, keeping in mind patient expectations and the potential risks and benefits of the procedure.”

  • The analysis by De Rosa et al was funded by the Italian Ministry of Education, University and Research (MIUR).
  • Shah and De Rosa report no relevant conflicts of interest.
  • Indolfi reports receiving grants from St. Jude Medical.