FDA Extends MitraClip Indication to Include Functional MR

The US Food and Drug Administration has extended the indication for the MitraClip (Abbott) to include heart failure (HF) patients who have moderate-to-severe functional mitral regurgitation (MR) despite treatment with optimal medical therapy.

The decision, announced today, comes in the wake of the 610-patient COAPT trial, presented at the TCT 2018 meeting, showing that transcatheter mitral valve repair using the percutaneous clip procedure in patients with heart failure and severe functional MR significantly reduced not only the primary endpoint HF rehospitalizations, but also mortality at 2 years.

“Expanding the approval of this device to heart failure patients with significant secondary mitral regurgitation, who have failed to get symptom relief from other therapies, provides an important new treatment option,” said Bram D. Zuckerman, MD, director of the Division of Cardiovascular Devices in the Center for Devices and Radiological Health at the FDA. “Careful evaluation by a team of specialists is essential to determining whether a particular patient is an appropriate candidate for this procedure.”

The expanded approval comes despite calls, by some, that a third “tie-breaking” trial was warranted, given the lack of benefit for MitraClip seen in the MITRA-FR trial. Indeed, a third trial is still ongoing, RESHAPE-HF 2. As reported by TCTMD, when COAPT and MITRA-FR were first released, investigators working in this space had very strong—and opposing—views on whether the FDA should wait for more evidence, or grant the extension.

As previously reported by TCTMD, in COAPT the primary efficacy endpoint—all hospitalizations over 24 months—was significantly lower in the MitraClip versus the medical care group. Annualized rates of hospitalizations were 35.8% versus 67.9%, respectively (P < 0.001), yielding a number needed to treat of 3.1. Results in per-protocol, intention-to-treat, and as-treated analyses were very similar to the overall findings. Freedom from device complications in the MitraClip group was 96.6%. Perhaps most strikingly, 2-year mortality, a powered, prespecified secondary endpoint, was significantly lower among MitraClip-treated patients at 29.1% versus 46.1% (HR 0.62; 95% CI 0.46-0.82), yielding a number needed to treat of 5.9.

In COAPT, death or rehospitalizations for heart failure, which was the primary endpoint in MITRA-FR (measured at 1 year in MITRA-FR and 2 years in COAPT), was 45.7% in the MitraClip group versus 67.9% in the medical therapy arm, again a statistically significant difference.

Lead investigator Gregg W. Stone, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), commented on the decision for TCTMD today.

“We are gratified that the FDA has quickly moved to grant an indication for MitraClip treatment of patients with heart failure and severe mitral regurgitation who remain symptomatic despite guideline directed medical therapy,” Stone said in an email. “As demonstrated in COAPT, this therapy offers the potential to substantially prolong survival, prevent hospitalization, and improve quality-of-life for tens of thousands of suffering patients.”

The FDA announcement today stressed that while 6.5 million American adults live with heart failure, it is a small percentage of these patients who also have moderate-to-severe or severe “secondary” mitral regurgitation. “With this new approval, this small percentage of patients could be indicated as candidates for treatment with the MitraClip device when combined with optimal medical therapy,” the FDA said.

The MitraClip was previously approved in 2013 for the treatment of degenerative (“primary”) mitral regurgitation, a far smaller proportion of the MR patient population.