FDA Circulatory System Devices Panel Assesses Atrial Septal Defect Occluders

May 24, 2012—The US Food and Drug Administration's (FDA) Circulatory System Devices Panel met to discuss the current knowledge regarding the safety and effectiveness of the Amplatzer septal occluder (St. Jude Medical, Inc., St. Paul, MN) and the Gore Helex atrial septic defect (ASD) occluder (Gore & Associates, Flagstaff, AZ) as transcatheter occluders used for the closure of secundum ASD. The Amplatzer device was introduced in the United States in the 2001, and the Helex device was introduced in 2006. The Circulatory System Device Panel's summary of the May 24th meeting is available on the FDA's website along with other relevant materials.

According to the FDA, with more widespread use of these devices, more information has become available regarding adverse events. These events range from rare life-threatening events to more common events that are perceived to have less severe clinical sequelae. The FDA panel noted that many of these events were evident in the premarket studies; however, rare events such as erosion were not seen.

The panel advised that the meeting was convened to discuss the significance of these events in the overall context of the disease and existing treatment options, to discuss whether additional measures should be taken to improve protection of the public health (eg, additional study and/or data analyses, labeling changes), and to communicate to patients and physicians what is and is not known about device treatment options.

As outlined in its summary, the panel discussed the clinical significance of erosion, fracture, embolization, and other adverse events in the context of disease, surgical alternatives, and benefits of device closure. The panel concluded that the overall known safety profile of this class of devices has not changed since marketing approval; however, awareness of the full spectrum of events/outcomes has been elucidated. Furthermore, the panel determined that there is insufficient information to confidently determine which patient subgroups are at increased risk for certain events associated with transcatheter ASD device closure.

The FDA's Circulation System Devices Panel reached the following consensus positions.

The panel agreed that the root cause of erosion events observed with the Amplatzer device has been incompletely characterized, and all risk factors are not known. The analyses to date seem to be reasonable, but there is insufficient data—including inadequate echocardiographic information—about the cases that have already been reported to determine etiology.

The panel concluded that ASD device placement increases the risk associated with future interventions, including mitral valve repair and electrophysiology procedures that require transseptal puncture. The panel believes that patient follow-up recommendations should be modified. Because events are more frequent in the first 12 months, it was recommended that there should be frequent follow-up during the first year (eg, serial echo at 1 week, 1 month, and 6 months) and clinical follow-up yearly with less frequent follow-up after the first year. Specific recommendations regarding clinical and imaging follow-up should be further vetted as the issue is further examined. Mandatory device tracking was strongly recommended for both devices (ie, the device class).

The panel agreed that the current instructions for use for the Amplatzer device should be modified so that the contraindication related to having a 5-mm anterosuperior aortic rim is clarified and changed to a warning. In the patient and physician labeling, both devices should include a warning regarding patient symptoms that require emergent treatment (eg, severe chest pain). Also, standard training of echocardiographers and standard imaging should be performed.

The panel believes that there is no need to reanalyze the data collected from the Helex studies. However, a reanalysis should be performed for the Amplatzer data collected, with suggestions to consider other variables not previously analyzed, use existing data on noncases (either from the premarket study or postapproval study) to estimate relative risk for events, and assess center volume and user experience.

The panel agreed that for both devices, the ongoing postapproval studies should remain unchanged. Also, it was agreed that a 522 study is indicated for the Amplatzer ASO device. A case cohort study design was suggested under the 522 regulation, with an additional suggestion that data on both devices be captured in prospective registries, possibly utilizing the American College of Cardiology/Society of Thoracic Surgeons framework. A majority of the panel members agreed that a 522 study for the Helex device to address fracture issues was not necessary.

Other panel recommendations in the FDA summary included that additional measures should be taken to ensure that patients are informed of the risks/benefits of transcatheter ASD closure, that patients should be informed by more robust preprocedural information so they are aware of risks/benefits before the procedure (and direct communication to patients who have already been implanted), and that communication should come from the FDA and the sponsors in the form of a letter generated by sponsors given to clinical sites and distributed to the patients.