PFO Closure Can Prevent Recurrent Cerebrovascular Events

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Percutaneous closure of patent foramen ovale (PFO) seems to be as good at preventing secondary strokes as medical therapy. Even better, it appears more effective than drugs alone at preventing recurrent transient ischemic attacks (TIAs). The results, from an observational study of patients with PFO-related index events, were published online January 11, 2012, ahead of print in Circulation.

For the study, Bernhard Meier, MD, of University Hospital (Bern, Switzerland), and colleagues prospectively followed 308 consecutive patients with cerebrovascular events presumably related to PFO with or without associated atrial septal aneurysm (ASA). Patients underwent either percutaneous PFO closure (n = 150) or medical treatment (coumarin or antiplatelet agents; n = 158) between 1994 and 2000. Each individual treatment decision was based on consensus between the neurologist and the patient. Median follow-up duration was 10 years (range, 8 to 15 years), adding up to a total of 1,582 patient years for PFO closure and 1,685 patient years for medical treatment.

Reduction Seen in TIAs, Not Stroke

Propensity score matching identified 103 pairs of patients. In this analysis, PFO closure was associated with a reduced risk of the primary composite endpoint of stroke, TIA, or peripheral embolism compared with medical treatment, although all-cause, cardiac, and vascular mortality were similar in both groups. The lower event rate in favor of percutaneous PFO closure was mainly due to a reduction in TIAs. None of the matched patients experienced peripheral embolism (table 1).

Table 1. Clinical Outcomes in Propensity Matched Cohort

 

PFO Closure

Medical Treatment

HR
(95% CI)

P Value

Cardiovascular Death

3%

3%

1.00
(0.32-3.10)

1.00

Stroke

6%

8%

0.75
(0.26-2.16)

0.59

TIA

5%

14%

0.31
(0.10-0.94)

0.039

Major Bleeding

1%

3%

0.33
(0.03-3.20)

0.34

Stroke, TIA, or
Peripheral Embolism

11%

21%

0.43
(0.20-0.94)

0.033


Multiple events occurred in 1 patient after PFO closure but in 11 patients given medical treatment (P = 0.006). In the medical treatment group, 33 of the 103 matched patients (32%) crossed over to subsequent percutaneous (n = 29) or surgical (n = 4) PFO closure.

Kaplan-Meier estimates showed that, at 15 years, the composite endpoint was less frequent in the PFO closure group (16.5% vs. 26.2%; P = 0.08). Major bleeding occurred in 1 patient in the PFO closure group (1.0%) and 3 patients in the medically treated group (2.9%; P = 0.34).

Although no treatment by subgroup interaction for presence or absence of ASA was noted, the researchers say it deserves further study.

Rounding out CLOSURE I

In the paper, Dr. Meier and colleagues suggest that their results are “mutually compatible” with those of the CLOSURE I trial, presented at the 2010 American Heart Association Scientific Sessions in Chicago, IL. CLOSURE I randomized 910 patients and found no significant difference between device closure and medical therapy at 2 years.

Dr. Meier explained to TCTMD in an email communication that the current study came close to achieving the CLOSURE I trial’s originally anticipated yearly event rate. Because a “suboptimal” device was used in CLOSURE I and the 2-year follow-up period of that trial was “too short,” he said, the final results of that trial could not significantly confirm the advantage of device closure in this patient group.

As for the more recent findings, Dr. Meier said that he was surprised by the low number of events experienced by patients in the medical treatment group but had expected “that those with a closed PFO had even fewer events, as paradoxical emboli are effectively prevented by PFO closure.”

While the neurology literature may overestimate the risk associated with PFO, some level of “risk is clearly there and it pertains to very significant events including stroke and death,” Dr. Meier asserted. “PFO closure is the easiest, safest, and technically most successful procedure in interventional cardiology and in my opinion it is highly underused around the world.”

‘A Little Bit Suspect’

However, lead author of the CLOSURE I trial, Anthony J. Furlan, MD, of Case Western Reserve University School of Medicine (Cleveland, OH), told TCTMD in a telephone interview that this study “typifies some of the issues we have to deal with in the field.” These include:

  • Being underpowered
  • Using too many different devices with varying procedural complications
  • Not discussing the differences between paradoxical embolism and cryptogenic stroke

“It has all the problems of nonrandomized trials,” he said. “The one nice thing that they did have was a long follow-up, but it’s very important to note that they use this combined endpoint of death, TIA, and stroke and even after 15 years, the only difference seen was with the TIA. So that’s not a particularly hard endpoint especially since they didn’t define TIA really rigorously in this manuscript.”

In general, relying on TIA for a study conclusion is “always a little bit suspect because it’s not a precise endpoint,” Dr. Furlan said, adding that CLOSURE I used a definition that was “independently adjudicated by an external reviewer.”

Not the Definitive Study

With regard to this study and CLOSURE I being ‘mutually compatible,’ Dr. Furlan said this makes sense in terms of the differing follow-up periods. However, he countered, “The conclusion of this study is [not] warranted by the data, nor is it supported by [CLOSURE I]. I would not use the findings of this study as justification for using device closure over medical therapy. I think that’s an over interpretation of the results.”

Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview that the newer study by Dr. Meier and colleagues provides valuable information, because it might take longer than 2 years—CLOSURE I’s follow-up duration—for differences between medical therapy and PFO closure to become evident.

“The importance of studies like this, even though they are never going to meet the [US Food and Drug Administration] criteria for approval for these procedures, is that there is evidence that there are patients out there who could benefit from this procedure. Our job now is figuring out who they are,” Dr. Sommer said. “It’s an interesting paper, and it just underscores the need for us to continue to look at this problem because we just don’t know the answers yet.”

Final results from CLOSURE I and another randomized event-driven study, RESPECT, are due to be published within the next year, Drs. Furlan and Sommer reported.

Study Details

Six closure device types were utilized according to historical availability: Amplatzer PFO (n = 54; St. Jude Medical, St. Paul, MN), PFO STAR (n = 42; Cardia, Eagan, MN), Sideris Buttoned (n = 27), Angel Wing (n = 10; Cardia), Amplatzer ASD (n = 9; St. Jude Medical), and CardioSEAL (n = 8; NMT Medical).

Patients undergoing percutaneous PFO closure were more likely to be hypercholesterolemic, to have a larger right-to-left shunt, and to have suffered more than 1 cerebrovascular event than patients undergoing medical treatment. Closure was successful in 148 patients (99%).

 


Source:
Wahl A, Juni P, Mono M-L, et al. Long-term propensity-score matched comparison of percutaneous closure of patent foramen ovale with medical treatment after paradoxical embolism. Circulation. 2012;Epub ahead of print.

 

 

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Disclosures
  • Dr. Meier reports receiving research grants and speaker fees from St. Jude-AGA Medical.
  • Dr. Furlan reports no relevant conflicts of interest.
  • Dr. Sommer reports being a physician trainer for AGA and Gore as well as serving on the medical advisory board for Coherex.

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