A new study—presented at the American College of Cardiology (ACC) Scientific Session (10–12 March, Orlando, USA) and published in the Journal of the American College of Cardiology—indicates that patients with “high-risk” patent foramen ovale (PFO), based on morphological characteristics, who underwent percutaneous PFO closure had a significantly lower risk of recurrent stroke than did patients who received medical therapy alone.
Writing in JACC, Pil Hyung Lee (Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) and others report that “high-risk” PFO—as defined by transoesophageal echocardiography (TEE)—includes size of the PFO, the presence of atrial septal aneurysm, or hypermobility. They add that, in a previous study, they found these factors were useful in predicting the risk of stroke recurrence. “Considering the high prevalence of PFO in the general population and in patients with cryptogenic stroke, transcatheter device closure confined to patients with cryptogenic stroke and characteristic PFO morphology associated with a higher stroke recurrence rate would be a more appropriate approach to enhance the benefits of PFO closure. To test this hypothesis, this multicentre, randomised, open-label trial was performed,” Hyung Lee et al comment.
In the study, of those who presented with cryptogenic stroke and high-risk PFO, patients were randomised to undergo percutaneous PFO closure (Amplatzer PFO Occluder, Abbott) or medical therapy (60 in each group). The primary endpoint was a composite of stroke, vascular death, or Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding during two years of follow-up.
After a median follow-up of 2.8 years, in the intention-to-treat cohort, no events occurred in the PFO group vs. six patients in the medication-only group (p=0.013). Hyung Lee at state: “The Kaplan-Meier two-year cumulative estimate of the probability of stroke was 10.5% in the medication-only group (p=0.0232 for the comparison with PFO closure group), which suggests that the number of people needed to treat to avoid one stroke at two years would be 10.”
Additionally, a per-protocol analysis found that primary events only occurred in the medication-only group in both groups and the event-free survival rates were significantly different (p=0.016 for the comparison).
The authors note that, recently, “we have witnessed the dramatic conversion from a negative to a positive outlook with respect to PFO closure. New trials with positive findings have a different study design in terms of medications and follow-up duration”. However they comment of the trial that showed a benefit for percutaneous PFO closure, only the CLOSE trial had “stringent entry criteria” similar to theirs. In CLOSE, patients had to have a large interarterial right-to-left shunt or an atrial septal aneurysm. Given that both CLOSE and the present study (DEFENSE-PFO) show no occurrence of stroke in patients who underwent PFO closure, Hyung et al say that their result suggest that “the beneficial effect of percutaneous device closure of PFO can be maximised by adding the morphologic characteristics of PFO, as evaluated by TEE, to the selection criteria for the procedure.”
They conclude: “We have confirmed that the morphologic characteristics of PFO and the adjacent atrial septa, as evaluated by TEE, are important determinants of the clinical benefit of percutaneous device closure of PFO in patients with cryptogenic stroke.”
Jae-Kwan Song (Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) presented the study during a late-breaking trial session at the ACC Scientific Session.
He told Cardiovascular News: “I feel it would be better to consider percutaneous device closure of a PFO only in cryptogenic stroke patients with high-risk PFO. Some may say it is too conservative, but I am sure many physicians believe it would be a better strategy considering the cost-benefit aspect. Although we did not include patients with low-risk PFO, the subgroup analysis of the previous trials (REDUCE and RESPECT) already confirmed that device closure is more favourable in patients with large PFO or PFO with atrial septal aneurysm and not in patients with small PFO, shunt or PFO without atrial septal aneurysm. Thus, I cannot recommend device closure in cryptogenic stroke patients without high-risk PFO.”