MitraClip Narrowly Passes Major Test With FDA Advisory Panel

March 21, 2013

Updated March 21 GAITHERSBURG,MD — The Food and Drug Administration (FDA) Circulatory System Devices panel narrowly gave its stamp of approval to the MitraClip (Abbott Vascular) clip delivery system today when it voted in favor of the device. Although the decision was not a vote of approvability per se, five of the eight voting panel members stated that the efficacy of the MitraClip exceeded the risks in patients deemed high risk for mitral-valve surgery.

The proposed indication for the MitraClip is for symptomatic mitral-regurgitation (MR>3+) patients deemed too high risk for open mitral-valve surgery by a cardiac surgeon and in whom existing comorbidities would not preclude the expected benefit from the correction of MR.

The advisory panel unanimously felt the MitraClip was safe but drew a tie-breaking vote from panel chair Dr Jeffrey Borer (SUNY Downstate Medical Center, New York NY) when it came down to the effectiveness of the device. In voting on efficacy, just four of the nine panel members felt there was a reasonable assurance that the MitraClip was efficacious in patients at high risk for surgery. On the whole, however, most felt that while the studies conducted by the sponsor had, as one panel member put it, "more holes in them than Swiss cheese," they did feel the risk/benefit ratio tipped in favor of the MitraClip.

Stating that he believes the benefits of the device exceed the risks, Dr Marc Katz (Bon Secours Heart and Vascular Institute, Richmond, VA) said the improvements in NYHA functional class in treated patients swayed his vote, as did some of the individual patients who've done well with the device.

"I have a hard time saying to patients, okay, we're going to wait another five years to have this available," said Katz. "In no way do I think this was an elegant study as I did with the PARTNER trial. I think it was really poor in a lot of ways. As I said earlier, I think we're put in a hard position here, but weighing the alternatives, and putting the patients up front here, was a deciding factor."

Other panelists agreed with Katz, saying that the data were formidable in terms of sorting out the benefits and the risks of the MitraClip.

Device Has Value for Selected Group of Patients

The FDA advisory panel spent the day analyzing the results of the Endovascular Valve Edge-to-Edge Repair Study (EVEREST II) and other registry data. The panel was particularly concerned about the use of retrospective analyses and registry data, namely the EVEREST II High-Risk Registry (HRR) and REALISM high-risk continued-access protocol, to identify a high-risk patient population that would receive benefit from the correction of MR with the MitraClip. In addition, the panel spent considerable time discussing the relative merits of comparing outcomes with a control group of propensity-matched patients from the Duke Database of Cardiovascular Disease (DDCD).

Dr Norman Kato (Cardiac Care Medical Group, Encino, CA) voted no on the issue of effectiveness, stating that he would like to see another study performed to be certain of the efficacy of the device in the intended patient population.

"I think there are enough patients who would satisfy the criteria for a randomized trial that it could be done quickly," said Kato. "I am concerned that we need to maintain at least some bar of scientific validity to ensure that we get some scientifically based assurance so that I can believe that these data are true."

Dr Michael Ferguson (National Naval Medical Center, Bethesda, MD) also voted no on the question of efficacy. "I think we'd really like to have this device available for people, and this is a pretty difficult decision," he said. "I think they just didn't do a good enough job defining a patient population that would benefit and in clearly establishing that the patients who received the device were not surgical candidates."

Similar sentiments were echoed by heart surgeon Dr Valluvan Jeevanandam (University of Chicago Medical Center, IL). "There are patients who will benefit from this device," he said. "I just hope it's not put into patients who would benefit from regular surgery. I think we should put as many safeguards as possible so that this doesn't happen and that this is put into a very small, restricted group of people who are truly inoperable."

As reported earlier this week by heartwire , FDA reviewers, who conducted their own analysis of the data, said the studies to date should be hypothesis-generating only and did not constitute valid scientific evidence of safety and effectiveness in the proposed population of inoperable MR patients [1]. The independent advisory panel largely agreed with the conclusions of the FDA review but felt the benefits of the MitraClip, especially for patients with zero surgical options, exceeded the low risks with the device.

The FDA is currently working with Abbott to develop a new study, known as COAPT . The open-label trial is designed so that physicians utilize the Society of Thoracic Surgeons (STS) risk score or surgeon assessment to determine the patient's risk for surgery. There will be a central eligibility committee to ensure that surgical risk is adequately documented by the surgeon when the STS score is less than 8% and that the patient has been adequately treated for heart failure. In total, 420 patients will be randomized; the primary end point is recurrent heart-failure hospitalizations. As of February 2013, just two patients have been enrolled in COAPT, according to Abbott.

The RESHAPE-HF trial is a European trial of patients with heart failure and functional MR. Approximately 800 patients are to be enrolled starting in mid-2013; the primary end point is a composite of all-cause mortality and recurrent heart-failure hospitalizations. The MitraClip has been available in Europe since 2008, when it gained CE Mark approval.

In a statement sent to heartwire from Abbott, Dr Charles Simonton, chief medical officer of Abbott's vascular division, said they are pleased with the outcome of the panel and look forward to continuing discussions with the FDA as it further assesses the MitraClip system.