Long-Term Results of a Randomized Trial Comparing Three Different Devices for Percutaneous Closure of a Patent Foramen Ovale - Trial Comparing 3 Devices for Percutaneous Closure of a PFO

Description:

The current trial sought to compare long-term outcomes after patent foramen ovale (PFO) closure with three commercially available closure devices: Amplatzer PFO/ASD occluder, Helex septal occluder, and CardioSEAL-STARflex.

Hypothesis:

Outcomes after percutaneous PFO closure would be different based on the type of device used.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • History of cryptogenic TIA or stroke
  • History of paradoxical embolism
  • Decompression sickness
  • Migraine

    Number of enrollees: 660
    Duration of follow-up: 5 years
    Mean patient age: 49.3 years
    Percentage female: 45%

Exclusions:

  • Active infective endocarditis, bacteremia, sepsis
  • Intracardiac mass (thrombus, vegetation, tumor)
  • Anatomy in which the device size required would interfere with other intracardiac or intravascular structures, such as valves or pulmonary veins
  • Thrombus in the venous pathway to the right atrium
  • Venous pathway, through which access to the defect is gained, is inadequate to accommodate the appropriate sheath size
  • Associated disease requiring heart surgery
  • Posterior, superior, inferior, (or anterior) rim, 5 mm
  • Patients unable to take antiplatelet or anticoagulant therapy
  • History of a severe allergy to nickel

Primary Endpoints:

  • Composite of TIA, stroke, or death from neurological causes or any other paradoxical embolism (including all periprocedural and in-hospital events)

Secondary Endpoints:

  • Stroke
  • Vascular death
  • Neurological events + complications requiring surgery

Drug/Procedures Used:

Patients with an indication for PFO closure were randomized in a 1:1:1 fashion to percutaneous closure with the Amplatzer PFO/ASD occluder, Helex septal occluder, or CardioSEAL-STARflex device. Devices were sized based on transesophageal echocardiogram.

Concomitant Medications:

All patients were prescribed 100 mg of aspirin and 75 mg of clopidogrel per day for the first 6 months after the procedure.

Principal Findings:

A total of 660 patients were randomized, 220 each to Amplatzer PFO/ASD occluder, Helex septal occluder, and CardioSEAL-STARflex. Baseline characteristics were fairly similar between the three arms. The qualifying diagnosis was cryptogenic stroke in 58%, transient ischemic attack (TIA) in 51%, migraine in 7.6%, and decompression sickness in 0.5%. Only 27% had a history of more than one ischemic event. Atrial septal aneurysms were noted in 28% in the Amplatzer arm, 43% in the Helex arm, and 37% in the CardioSEAL-STARflex arm. The mean PFO diameters were between 9.3 and 9.7 mm.

Device implantation for PFO closure was technically successful in all interventions. Most placement attempts were needed in the Helex group. In seven patients, the occluders were retrieved before release and exchanged for another Helex due to an unsatisfactory constitution. The longest procedural and fluoroscopic times were in the Helex group (33.5 ± 14.2 minutes [min]; 6.6 ± 4.6 min), although these differed only slightly compared with the other groups (Amplatzer: 28.6 ± 13.2 min, 4.1 ± 3.4 min; CardioSEAL-STARflex: 31.4 ± 12.2 min, 4.9 ± 3.5 min).

At 5 years, the highest closure rate was noted with Amplatzer devices (100%) and lowest with Helex (96.8%). Implantation of a second device was also more common with the Helex device. The primary endpoint of TIA, stroke, cerebral death, or paradoxical embolism was 3.8% for all devices combined (1.4% for Amplatzer, 4.1% for Helex, and 5.9% for CardioSEAL-STARflex; p = 0.042). This was primarily driven by a lower risk of TIA with Amplatzer (0% vs. 1.8% vs. 2.7%, p = 0.06) and stroke (0.9% vs. 1.8% vs. 2.7%, p = 0.36). Thrombus formation on the device was very common with the CardioSEAL-STARflex device (0% vs. 0.5% vs. 5%, p < 0.0001), as well as atrial fibrillation (AF) (3.6% vs. 2.3% vs. 12.3%, p < 0.0001). Device embolization was only noted in the Helex arm (1.4%).

Interpretation:

The results of the current trial indicate that there are significant differences between the efficacy of commercially available PFO closure devices (CardioSEAL-STARflex is however no longer available, as the company declared bankruptcy). The Amplatzer PFO/ASD occluder has the highest success rate and lowest rate of TIA/stroke. Although they have a low incidence, the highest rate of procedural failures and device embolization is associated with the Helex device. The CardioSEAL-STARflex device has the highest risk of thrombus formation, AF, and recurrent neurological events.

These are interesting findings, and may explain the discrepancies between the CLOSURE I (which used the STARFlex device) and RESPECT/PC trials (which used the Amplatzer device), although all three trials failed to show superiority over medical therapy for cryptogenic strokes. A few caveats are worth noting. First, the current trial included patients with migraine and TIA, which may have artificially lowered the event rate during follow-up, as their risk of recurrent stroke is lower than in people with a cryptogenic stroke at baseline. Paradoxically, the age range in this trial was wide (18-84 years). It is likely that cerebrovascular accidents in older patients were not cryptogenic, but due to other common risk factors. Including them in this trial may thus have artificially elevated the event rate during follow-up. Next, only about one quarter of patients presented with a recurrent ischemic event; the rest had one event only. Also, follow-up neurological events were clinically determined, not based on neuroimaging. Most importantly, this trial does not provide any further insights with respect to the merits of PFO closure versus medical therapy. That question remains largely unresolved.

References:

Hornung M, Bertog SC, Franke J, et al. Long-term results of a randomized trial comparing three different devices for percutaneous closure of a patent foramen ovale. Eur Heart J 2013;Jul 9:[Epub ahead of print].

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Noninvasive Imaging, Congenital Heart Disease, CHD & Pediatrics and Imaging, CHD & Pediatrics and Quality Improvement, Echocardiography/Ultrasound

Keywords: Stroke, Ischemic Attack, Transient, Follow-Up Studies, Foramen Ovale, Patent, Risk Factors, Neuroimaging, Thrombosis, Decompression Sickness, Migraine Disorders, Embolism, Paradoxical, Echocardiography, Transesophageal, Septal Occluder Device


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