Two Afib Ablation Devices Up for FDA Panel Review
By Emily P. Walker, Washington Correspondent,
Reviewed by
October 25, 2011
Review
WASHINGTON -- One cardiac ablation device appeared safe and worked well to restore normal heart rhythm in atrial fibrillation patients during surgery, while a separate ablation system posed some troubling safety risks, FDA staff wrote in two separate reviews released this week.
The agency's Circulatory System Devices Panel meets Wednesday to discuss and vote on AtriCure's Synergy Ablation System and again on Thursday to discuss and vote on the approvability of Medtronic's Cardiac Ablation System.
First up: AtriCure's device, which is already approved for ablation of heart tissue during surgery. According to briefing documents posted by AtriCure, the device is already used off-label in a procedure called Maze IV, in which a heart surgeon creates cardiac lesions during open-heart surgery or valve surgery in patients that also have atrial fibrillation.
But since the device's current label doesn't mention atrial fibrillation, AtriCure can't train doctors on how to use the device to achieve heart rhythm control or discuss atrial fibrillation in any way, so the company is seeking expanded approval to indicate the device should also be used to restore normal heart rhythm in patients with atrial fibrillation.
The FDA's panel of outside cardiac experts will review AtriCure's ABLATE trial, which examined the outcomes of 55 patients with atrial fibrillation, all of whom received surgery.
The study size was very small, making it difficult to draw firm conclusions. But as the FDA pointed out, it's challenging to get adequate enrollment in larger, randomized atrial fibrillation trials because neither investigators nor patients are willing to face the potential of being randomized to treatment with drugs when the patient was already scheduled for surgery to treat atrial fibrillation.
In the ABLATE trial, 74% of the patients met the primary endpoint of having no episode of atrial fibrillation that lasted longer than five minutes (at least 60% of patients had to meet that endpoint for the study to be considered a success by the FDA).
However, there were four patients with paroxysmal or intermittent atrial fibrillation, so they may have been healthier than persistent atrial fibrillation patients. When those patients are included in the analysis, the primary endpoint is just missed, the FDA said.
As for safety, 50 of the 55 patients had some sort of adverse event six months after surgery; six events were considered major adverse cardiac events. One patient had a stroke, and four patients died. Those rates are to be expected, the FDA said.
"There appears to be no safety signal in this limited cohort of patients," the FDA reviewers wrote.
Wednesday's panel will vote on whether the benefits outweigh the risks for expanding the indication of the ablation system to treat patients with atrial fibrillation.
On Thursday, the panel will turn its attention to a separate atrial fibrillation device: Medtronic's Cardiac Ablation System, which is indicated for the treatment of symptomatic, drug-refractory, persistent atrial fibrillation.
The panel will review Medtronic's TTOP-AF (Tailored Treatment of Persistent Atrial Fibrillation) trial, which involved 210 atrial fibrillation patients randomized to receive either treatment with the ablation system or one of several anti-arrhythmic drugs.
After six months, 56% of patients in the catheter group had fewer heart irregularities, compared with only 26% in the medication group.
But the study revealed troubling safety issues: slightly more than one in five patients had a serious side effect shortly after surgery, including stroke, heart failure, and pneumonia. Five patients experienced a stroke within one month of having the procedure, while no patients in the medication arm had a stroke after six months.
In addition, the FDA reviewers pointed to three recently-published papers reporting that one of the catheters used in Medtronic's ablation system was linked to a 38% to 42% incidence of new asymptomatic cerebral embolic lesions identified on postprocedural MRI after the catheter was used for pulmonary vein isolation for the treatment of atrial fibrillation.
"FDA is concerned about the overall safety profile of the system," FDA reviewers concluded, adding that 38 out of 176 patients experiencing a serious device-or-procedure-related event is too high.
In Medtronic's briefing document, the company wrote its clinical trail "demonstrated the effectiveness of the system while providing a reasonable assurance of safety in the treatment of adult subjects with drug-refractory, symptomatic, persistent AF."
At the end of Thursday's meeting, the panel of cardiac experts will vote on the safety and effectiveness of Medtronic's device.
The FDA is not required to follow the advice of its advisory committees, but it often does.