Real-world Data Show MitraClip Benefit in COAPT-Ineligible Patients

LONDON, England – Fewer than one in seven patients with secondary mitral regurgitation (MR) would be eligible for transcatheter mitral valve repair with MitraClip (Abbott) based on the eligibility criteria outlined in the COAPT trial, according to a new real-world analysis from a large tertiary-care center.

While the vast majority of patients weren’t eligible for the device, mainly because they weren’t on guideline-directed medical therapy, the COAPT-ineligible patients who were ultimately treated with MitraClip had similar rates of death at 1 year when compared with COAPT-eligible patients who also received the percutaneous clip.

In contrast, COAPT-ineligible patients who were treated with medical therapy fared significantly worse than ineligible patients who received the device.

Lead investigator Eduardo Zancanaro, MD (San Raffaele Hospital, Milan, Italy), who presented the new data at PCR London Valves, told TCTMD the differences in the 1-year outcomes were quite striking and suggest that “COAPT was too strict in its criteria.” He noted that COAPT-ineligible individuals treated with guideline-directed medical therapy had a better clinical and echocardiographic profile than COAPT-ineligible patients who received the device, yet “those treated with medical therapy had much worse survival at 1 year compared with the patients treated with MitraClip,” he said.

Philippe Généreux, MD (Morristown Medical Center, NJ), who moderated the session and participated in COAPT, said a large number of patients in the trial were excluded because they improved when medical therapy was optimized. At his center, physicians were extremely aggressive with medical therapy, he said, and this included discussions with the heart team, including a heart failure (HF) doctor, before considering them eligible for trial.

The COAPT inclusion criteria has been put forward as one of the potential reasons why the results differed so drastically from the European MITRA-FR study. In COAPT, investigators randomized 614 patients with symptomatic HF, moderate-to-severe or severe secondary MR, and LVEF ≥ 20% to percutaneous mitral valve repair with MitraClip plus optimal medical therapy or to optimal medical therapy alone. Zancanaro said the stringent enrollment criteria for COAPT has been a hot topic since the trial was published.

“At the end of a trial, it’s very important to see how you can manage when you deal with patients in the real world,” he said. “How applicable is the criteria in real life?”

COAPT, which was presented at TCT 2018 and published simultaneously in the New England Journal of Medicine, showed that transcatheter mitral valve repair with MitraClip significantly reduced the primary endpoint of HF rehospitalizations, as well as mortality at 2 years. In the MITRA-FR trial, however, there was no difference in the risk of all-cause death and unplanned rehospitalizations for HF among patients treated with MitraClip and those treated with medical therapy.

Including, but Mostly Excluding, Patients With Secondary MR

Between January 2016 and May 2018, Zancanaro and colleagues identified 292 patients with secondary MR treated at their institution. Of these, 66 were excluded based on the severity of MR while another 40 patients were referred for surgery.

For the remaining 186 patients with secondary MR unable to undergo mitral-valve surgery, 149 would have been considered ineligible for COAPT. Inadequate medical therapy, LVEF less than 20% (or greater than 50%), and anatomy were most common reasons patients would have been excluded. This left 37 patients eligible for MitraClip based on the COAPT criteria (all 37 received the device). For the 149 patients who didn’t meet the COAPT inclusion criteria, 108 were treated with MitraClip, 30 were treated with medical therapy, and 11 patients underwent transcatheter mitral valve replacement.

At 1 year, COAPT-ineligible patients who were ultimately treated with MitraClip had significantly better outcomes than the ineligible patients treated with medical therapy. In total, 83.3% of patients ineligible for COAPT who received guideline-directed medical therapy were alive at 1 year compared 90.7% of COAPT-ineligible patients who received the device (P < 0.001). Survival at 1 year among the COAPT-eligible patients who received the MitraClip was 91.9%, which was not statistically different than trial-ineligible patients who also received the device (P = 0.573).

Jean-François Obadia, MD (Hôpital Cardiovasculaire Louis Pradel, Bron, France), the lead MITRA-FR investigator, has previously suggested that their trial represented more “real-world” practice than COAPT. To TCTMD, Zancanaro noted that while MITRA-FR suggested equivalent results with medical therapy and MitraClip in secondary MR, “for us the results are not the same.”

MitraClip has been in use for over a decade in Europe and the United States on the basis of randomized trials conducted in patients with primary (degenerative) MR. The US Food and Drug Administration expanded the indication for MitraClip in the US, back in March, to heart failure patients who have moderate-to-severe functional MR despite treatment with optimal medical therapy.

In Europe, percutaneous edge-to-edge repair in patients with secondary MR is a class IIb indication (level of evidence C).

Zancanaro stressed that patients with secondary MR are referred to their heart team for evaluation, and while they try to adhere to the COAPT eligibility criteria, they aren’t zealots in that regard. “We really think that the criteria trial should be followed, but not so strictly,” he said. “MitraClip is really a good device and we should be implemented in some way in secondary MR because it really gives good outcomes.”