FDA Advisory Panel Recommends, and FDA Approves, Bipolar Radiofrequency Clamp for Concomitant Surgery for Persistent Atrial Fibrillation
- Summary: An FDA advisory panel concluded that the benefits outweighed the risks when using the Synergy bipolar radiofrequency clamp during open heart surgeries for treating persistent and longstanding persistent atrial fibrillation. FDA approval was granted December 16, 2012.
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December 16, 2011 — Update: The Food and Drug Administration (FDA) formally approved the AtriCure Synergy Ablation System for the treatment of persistent and longstanding persistent atrial fibrillation in patients undergoing another heart surgery. The approval was based on results from the ABLATE clinical trial, which are discussed below. The approval came earlier than expected, and the Synergy bipolar radiofrequency clamp is the only surgical ablation device that has specific FDA approval for afib treatment. The approval allows the company to commence the surgeon training program discussed below.
November 9, 2011 — An FDA advisory panel concluded that the benefits of the AtriCure Synergy Ablation System outweighed the risks when used for treating persistent and longstanding persistent atrial fibrillation during concomitant open heart surgeries. Concomitant surgery is when afib ablation is performed during another heart surgery, such as coronary bypass grafting or valve replacement.
The Synergy Ablation System consists of the bipolar radiofrequency Synergy ablation clamp and a sensing unit that delivers radiofrequency energy to the clamp. To date, it has been used in over 100,000 ablations performed during open heart surgery. However, surgeons cannot receive training on how best to use it to treat afib because the FDA has only approved it for soft cardiac tissue, not atrial fibrillation.
Based on results from its ABLATE (AtriCure Bipolar Radiofrequency Ablation of Permanent Atrial Fibrillation) clinical trial, AtriCure is seeking FDA approval for the use of the bipolar radiofrequency clamp specifically for treatment of persistent and longstanding persistent atrial fibrillation during open heart surgeries. Such approval would allow the company to market the device for afib treatment and to start a formal training program for surgeons.
The FDA convened an advisory panel on October 26, 2011, to review and discuss results from the ABLATE trial and to recommend whether the agency should approve the bipolar radiofrequency clamp. The FDA often asks for input from an advisory panel when approval would represent the first-ever FDA approval for a device or treatment. In this case, the Synergy clamp would be the first FDA-approved product to treat atrial fibrillation during open heart surgeries.
ABLATE Clinical Trial Design and Results
The ABLATE clinical trial enrolled 55 patients with atrial fibrillation to receive ablation of cardiac tissue with the Synergy bipolar radiofrequency clamp while undergoing another heart surgery, such as coronary artery bypass or valve replacement or repair. Surgeons used the Synergy clamp to scar tissue in the Maze IV lesion pattern, which includes ablating tissue in both the left and right atria. Surgeons had the option to use another device, such as a radiofrequency multi-functional pen or a cryoablation probe, to ablate hard-to-reach areas of the heart.
The ABLATE clinical trial was designed using a Bayesian statistical method. A Bayesian design is often used when patients are not randomized between two arms, control and treatment, in a study. Since there is no control arm against which to compare a treatment’s safety and effectiveness, a Bayesian-based clinical trial’s endpoints are based on performance goals.
ABLATE’s effectiveness endpoint was based on a performance goal of 70% of patients being free of afib and off antiarrhythmic medication at six months. ABLATE’s safety endpoint was based on a performance goal of a major adverse event rate of 13.95%.
Dr. James Edgerton, of The Heart Hospital Baylor Plano in Texas, presented the results of the ABLATE clinical trial to the FDA advisory panel. ABLATE met its effectiveness endpoint, with 74% of patients free from afib and off antiarrhythmic drugs at six months. By type of surgery, 78% of patients who underwent coronary bypass were off antiarrhythmic medication at six months, as were 92% of patients who had had a valve procedure. Treatment also had a positive effect on patients’ quality of life. By 12 months, nearly 59% of patients characterized their cardiovascular health as “excellent” or “very good” and 33% as “good”.
In terms of safety, the ABLATE clinical trial used a composite of different complications to approximate the overall risk of treatment. The composite included the number of deaths, strokes, transient ischemic attacks (mini strokes), heart attacks, or instances of excessive bleeding experienced within 30 days of the procedure.
The ABLATE clinical trial also met its safety endpoint, with a major adverse event rate of 9.1%. This number may seem high but it primarily reflects the small number of patients in the study. In total, there were two deaths, one stroke, and two major bleeds during the 30-day period following treatment. None of these adverse events was related to the Synergy clamp. One death resulted from excessive bleeding related to the ablation procedure. The other death in the study was related to the general heart surgery.
Dr. Patrick McCarthy, of Northwestern University in Illinois, provided context for these complications using data from the Society of Thoracic Surgeons’ database, which tracks outcomes on 85% of all heart surgeries performed in the United States. Specifically, ABLATE’s operative mortality rate was 3.6% versus 3.7% in the surgical database. ABLATE’s stroke rate was 2.0% versus 1.9% in the database. The excessive bleeding rate was 3.8% in ABLATE versus 4.3% in the Society’s database. In addition, there were no instances of transient ischemic attack or heart attack in the ABLATE clinical trial, whereas the Society of Thoracic Surgeons database shows that 0.5% of patients have a transient ischemic attack and 1.5% of patients have a heart attack within 30 days of heart surgery.
Surprisingly, 12 patients in the ABLATE clinical trial needed to have a pacemaker implanted prior to hospital discharge. It’s not clear whether the need for a permanent pacemaker resulted from the ablation procedure, dysfunction related to the duration of patients’ afib, or another factor. When a patient has had atrial fibrillation for many years, the sinus node, which activates the electrical impulses in the heart, often does not work properly, and it may take time following afib surgery for the sinus node to fully recover function. At follow up, all patients had normal sinus node function and no longer needed a pacemaker.
Surgeon Training and Post-Approval Study
AtriCure indicated to the FDA advisory panel that there are approximately 1,000 surgeons in the US who use the bipolar radiofrequency clamp in concomitant afib surgeries. However, not all of the surgeons ablate tissue according to the Maze IV bi-atrial lesion pattern. The company has made a commitment to train all current and new users on both the Synergy clamp as well as on the Maze IV. Surgeons will have to undergo a robust training program and achieve at least a 90% score on the final proficiency exam to become certified on the Synergy clamp. This is good news for patients, as training and operator experience have been shown to improve patient outcomes for most procedures, including afib surgery.
AtriCure has also proposed conducting a post-approval study, which will enroll up to 350 patients with persistent or longstanding persistent afib at up to 50 hospitals across the US. This would add to clinical data available on outcomes associated with treatment of more severe forms of afib. It could also provide key information on what should be added to AtriCure’s training program to improve patient outcomes.
Panel Vote and Recommendations
The FDA advisory panel voted unanimously that the Synergy bipolar radiofrequency clamp was effective in treating patients with persistent and longstanding persistent afib. In terms of safety, the panel voted five to four, with one abstention, that the ABLATE data provided reasonable assurance that the Synergy clamp was safe. Overall, the panel voted five to three, with one abstention, that the benefits of AtriCure’s Synergy clamp outweighed the risks in treating patients with persistent and longstanding persistent afib.
The FDA is not obligated to follow an advisory panel’s recommendations but often does. The FDA had some concerns about the ABLATE clinical data and its “interpretability” to a wider patient population, since only 55 patients were enrolled in the study. In addition, four of the patients were later deemed by independent reviewers to have paroxysmal atrial fibrillation. FDA representatives expressed concern that the four paroxysmal patients may have been healthier than the persistent or longstanding persistent afib patients in the study, which could have made the Synergy clamp’s safety appear better than it is. Presumably, the FDA and AtriCure will continue their discussion of the safety events recorded in the trial and to what extent AtriCure’s proposed surgeon training program can reduce the number of complications.
In general, the FDA representatives at the panel meeting seemed supportive of AtriCure’s proposed post-approval study. However, the FDA and AtriCure may have to decide on the performance goals, such as the percentage of patients free of afib and off antiarrhythmic drugs, to set for the post-approval study.
AtriCure now expects to receive formal FDA approval for the Synergy bipolar radiofrequency clamp to treat persistent and longstanding persistent atrial fibrillation in patients undergoing open heart surgery by the end of March 2012. The company believes all surgeons who currently use the Synergy clamp could complete AtriCure’s training program within 18 months of formal FDA approval.
See related information:
- Dr. James Edgerton Discussing Treatment Options — Video
- Maze Procedure—Surgical Ablation
- Are You a Candidate for Surgical Ablation?
- AtriCure Executive Summary of Synergy Ablation System for Advisory Panel
Disclaimer: Patients come first at StopAfib.org, and we do not compromise on that. For transparency, we note that StopAfib.org has received grants from AtriCure to support our patient education efforts. This article was written by an independent observer and was not reviewed by the company.