Studies Evaluate Outcomes of Transcatheter PFO Closure

July 11, 2013—Two evaluations of transcatheter patent foramen ovale (PFO) closure were recently published online ahead of print in the European Heart Journal.

In the first study, Pablo Rengifo-Moreno, MD, et al conducted a systematic review and meta-analysis of randomized controlled trials studying the effect of transcatheter PFO closure versus medical therapy on recurrent vascular events. In the second study, Marius Hornung, MD, et al presented long-term results from a randomized trial comparing three different devices for percutaneous closure of a PFO. 

Dr. Rengifo-Moreno and colleagues noted that in patients with cryptogenic stroke, transcatheter closure of a PFO has not been shown to better prevent recurrent vascular events than medical therapy; however, randomized controlled trials to date have included few vascular events, and lack of power has been raised as an important concern.

As summarized in the European Heart Journal, the investigators searched Medline, Pubmed, Embase, and Cochrane databases for the search terms “patent foramen ovale,” “PFO,” “stroke,” “percutaneous closure,” and “transcatheter closure” from inception through April 2013, with no language restrictions. Only studies in adult humans were considered. Additional references were obtained from the bibliographies of the studies reviewed. The following criteria were used for study selection: (1) randomized controlled trial; (2) subjects were adult patients with cryptogenic stroke who were randomized to transcatheter PFO closure or medical treatment—antiplatelet therapy and/or anticoagulation; and (3) reported outcomes included cardiac death, all death, stroke, transient ischemic attacks (TIAs), and peripheral embolism.

The investigators stated that methodological and descriptive data, adverse events (including raw data and risk estimates), as well as procedural success and complications were abstracted in duplicate from each study independently, and agreement was tested. The investigators advised that they rigorously followed the recommended guidelines for reporting, conducting, and assessing meta-analyses of randomized controlled trials. The primary endpoints prespecified in advance were recurrent vascular events and a composite endpoint of death and recurrent vascular events.

The investigators reported that three studies were identified as meeting selection criteria. These included a total of 2,303 patients, with 1,150 patients randomized to transcatheter PFO closure and 1,153 patients randomized to medical therapy. Mean follow-up was 3.5 years. Baseline characteristics (age, sex, and cardiovascular risk factors) were similar across studies. Intention-to-treat analyses showed a statistically significant risk reduction in stroke and/or TIA in the transcatheter PFO closure group when compared to medical treatment (pooled hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36–0.97; P = .04). The combined outcome of death and vascular events showed a borderline statistically significant benefit for transcatheter PFO closure when compared to medical treatment (pooled HR, 0.67; 95% CI, 0.44–1; P = .05). Subjects with a substantial PFO shunt seem to benefit the most with transcatheter PFO closure (pooled HR, 0.35; 95% CI, 0.12–1.03; P = .06); however, it did not reach statistical significance.

Dr. Rengifo-Moreno and colleagues concluded that these results suggest that in patients with cryptogenic stroke, transcatheter PFO closure may be beneficial in reducing the risk of recurrent vascular events when compared to medical treatment. They advised that the benefit of transcatheter PFO closure may be greater in patients with a substantial shunt.

In the second European Heart Journal article, Dr. Hornung and colleagues conducted a prospective comparison of procedural complications and long-term results after PFO closure in patients with cryptogenic stroke who were randomized to three different closure devices. The three devices were the Amplatzer PFO occluder (St. Jude Medical, Inc., St. Paul, MN), the Gore Helex septal occluder (Gore & Associates, Flagstaff, AZ), and the CardioSeal-StarFlex (NMT Medical, Inc., Boston, MA). Gore & Associates acquired the assets and intellectual property of NMT Medical in October 2011.

As summarized in the European Heart Journal, 660 patients with cryptogenic stroke were randomized to the three different closure devices with 220 patients per group between January 2001 and December 2004. The primary endpoint was defined as recurrent cerebral ischemia (stroke, TIA, or amaurosis fugax), death from neurological cause, or any other paradoxical embolism within 5 years after the index procedure.

The investigators reported that device implantation was technically successful in all interventions (n = 660; 100%). The procedure was complicated by pericardial tamponade requiring surgery in one patient (Amplatzer group) and device embolization in three patients (all Helex group). Thrombus formation on the device was detected in 12 cases (11 with CardioSeal-StarFlex, one with Helex, and none with Amplatzer; P < .0001), of which two required surgery. Complete closure after single-device implantation was more common with Amplatzer and with CardioSeal-StarFlex than with the Helex occluder (Amplatzer vs Helex vs CardioSeal-StarFlex: n = 217 [98.6%] vs n = 202 [91.8%] vs n = 213 [96.8%]; P = .0012).

Within 5 years of follow-up, the primary endpoint occurred in 25 patients (3.8%; 10 TIAs, 12 strokes, and three cases of cerebral death). Compared with the CardioSeal-StarFlex, (6%; six TIAs, six strokes, one cerebral death) and Helex groups (4%; four TIAs, four strokes, one cerebral death), significantly fewer events (P = .04) occurred in the Amplatzer group (1.4%; two strokes, one cerebral death).

Dr. Hornung and colleagues concluded that although procedural complications and long-term neurological event rates are low, regardless of the device used, the recurrent neurological event rate was significantly lower after Amplatzer than after CardioSeal-StarFlex or Helex implantation. This has important implications regarding the interpretation of trials comparing PFO closure with medical management, advised the investigators.