GAITHERSBURG, MD. – A Food and Drug Administration Advisory panel on Oct. 27 did not support the approval of a catheter-based radiofrequency ablation device for treating persistent atrial fibrillation, citing concerns over safety issues.
At the meeting, the FDA’s Circulatory System Devices Panel voted 8 to 2 that the data on the Medtronic cardiac ablation system did not demonstrate that the benefits outweighed the risks of the device for the proposed indication: the treatment of symptomatic, drug refractory, persistent atrial fibrillation (AF) or long-standing persistent AF of up to 4 years in duration. Panelists described it as a pioneering and innovative device that was effective in a difficult-to-treat population and unanimously voted that there was "reasonable assurance" that it was effective for the proposed indication.
But they voted 9 to 1 that there was not reasonable assurance that it was safe, primarily because of the increased rate of strokes around the time of the procedure (3% compared to none among those treated medically in the medical treatment arm of the pivotal study) and the 4% rate of pulmonary vein stenosis and symptomatic narrowing of the pulmonary vein 6 months after treatment with the device (4%).
Panelists were also concerned about reports in the literature of asymptomatic cerebrovascular emboli in patients treated with the device, which has been available in Europe since 2006, where it is approved for the treatment of paroxysmal atrial fibrillation. (Patients in the pivotal trial were not evaluated for asymptomatic cerebrovascular emoboli.)
The components of the catheter-based device include an RF ablation generator and three cardiac ablation catheters, a unique feature for this kind of device. The pulmonary vein ablation catheter is designed to create lesions in the left atrium, the "Multi-Array Septal Catheter" is designed to create lesions on the septal wall of the left atrium, and "Multi-Array Ablation Catheter" is designed to create lesions in the left and/or right atrium.
In the pivotal study, a prospective multicenter study of 210 patients with a history of symptomatic, refractory AF who had failed at least one class I or III anti-arrhythmic drug, patients were randomized to treatment with the device or medical treatment, in a 2:1 ratio. Their mean age was about 60 years and most were men, and had had AF for 4 months to 6 years. The exclusion criteria included having received prior ablation for AF, structural heart disease, NYHA class III or IV, LVEF under 40%, and a history of stroke or TIA.
The primary end point of the study – acute procedural success and at least a 90% reduction in clinically significant AF/atrial flutter on 48-hour Holter at 6 months – was met by 56% of those treated with the device, compared with 26% of those who were medically managed, a statistically significant difference.
The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.