MUNICH — Treatment with the MitraClip device on top of optimal medical therapy failed to shift outcomes in MITRA-FR, the first prospective randomized study to examine percutaneous mitral-valve repair in patients with functional mitral regurgitation (MR).
At 1 year, there was absolutely no difference in the primary composite endpoint of all-cause death or unplanned hospitalization for heart failure (HF) between the MitraClip and medical therapy-alone groups (odds ratio [OR], 1.16; P = .53).
This lack of benefit was consistent for the individual components of the endpoint and in per protocol analyses.
While the study confirmed prior observations that the MitraClip is safe and effective, it was unable to show that correction of functional MR changes the prognosis, Professor Jean-François Obadia, MD, Louis Pradel Hospital, Bron Cedex, France, said in a hotline session at the European Society of Cardiology (ESC) Congress 2018.
"This leads us to think that very probably the main cause of the disease is more the underlying cardiomyopathy and that the mitral regurgitation is more a marker of [severity] than a cause of the disease," he said.
Studies such as COAPT, to be presented next month at the TCT 2018 meeting, as well as RESHAPE-HF and MATTERHORN, will provide further insights, but observers, and no doubt industry, were looking for a better start for percutaneous mitral repair in functional or secondary MR — a setting that holds a dominant position in many countries despite the lack of randomized data.
The MitraClip system (Abbott Structural Heart) was approved in the United States in late 2013 for the treatment of symptomatic degenerative MR in patients considered at high risk for mitral valve surgery. European guidelines offer a weak class IIb level C recommendation that a percutaneous edge-to-edge procedure may be considered in patients with secondary MR, Obadia said.
To fill the evidence gap, investigators evenly assigned 307 patients with severe secondary MR, a left ventricular ejection fraction between 15% and 40%, and New York Heart Association functional class 2 to 4 to optimal medical therapy alone or with percutaneous MitraClip repair. Three patients were excluded after randomization, leaving 152 patients in each arm.
Device implantation was not attempted or failed in 14 patients (9.2%) and was successful in the remaining 138 patients (96%).
During the procedure, 14.6% of patients had periprocedural complications, including hemorrhage resulting in transfusion or surgical intervention in five patients, cardiogenic shock requiring inotropic support in four, atrial septum lesion or atrial septal defect in four, cardiac embolism in two, and cardiac tamponade in two.
At hospital discharge, however, 92% of 123 patients in the intervention group with MR severity assessments had a reduction in MR to 2+ (mild or moderate) or lower.
At 12 months, 37 patients in the intervention arm and 34 patients in the control arm had died. The composite primary outcome had occurred in 54.6% and 51.3%, respectively.
Secondary analyses showed no interaction between treatment and any subgroup with regard to the primary endpoint.
"There is room for more new prospective randomized studies because we cannot exclude that in a subgroup of patients the MitraClip could be efficient," Obadia said.
Invited discussant Stephan Windecker, MD, Bern University Hospital, Switzerland, said the trial was underpowered to detect smaller differences in the primary endpoint and that data were incomplete on secondary endpoint assessment, including brain natriuretic peptide, functional status, and quality of life; on subgroup analyses of MitraClip responders; and on tricuspid regurgitation and right ventricular function, which affect prognosis. Paired echocardiographic data were also incomplete.
"This information is important to explain the disconnect between the efficacy in reducing MR on one hand and the large treatment effect that actually has been observed in the conservative treatment group, which in a sense speaks to the excellent medical treatment," he said.
Windecker's interpretation of the trial is that "prognosis is determined by the underlying cardiomyopathy; guideline-directed medical therapy, including CRT when indicated is the standard of care; however, the heart team is empowered to consider the MitraClip as palliative therapy in selected patients who remain highly symptomatic despite medical therapy."
The results were published simultaneously in the New England Journal of Medicine.
To Clip or Not to Clip
Observers had mixed reactions to the results and whether they should curb the increasing use of MitraClip in functional MR.
"I think this should change practice; I think it should rock people's world a little bit," Athena Poppas, MD, Brown University, Providence, Rhode Island, commented to theheart.org | Medscape Cardiology. "It comes back to believing something should work but testing it in the correct way with a randomized trial to prove that point. We've seen this again and again."
Come Monday morning, Poppas said, "Given the procedural complications that occur in the best of hands, you should not be performing this in functional mitral regurgitation. We have excellent medications with a low side effect profile, and why would you put a patient through a procedure with a 14% complication rate when there's no clear benefit?"
"Now if they come up with quality-of-life data at 12 months, you would have to tell your patient they might feel better but they won't live longer."
Windecker disagreed. "I think at this point in time we need to collect more data and certainly with COAPT, there is no reason to halt everything but rather to digest the data, to reflect on the data, and to await the data from COAPT, where potentially with patients who are not as extreme risk the intervention may have some impact."
Commenting to theheart.org | Medscape Cardiology, COAPT co-principal investigator Michael Mack, MD, Baylor Health Care System, Dallas, Texas, said, "The results are extremely disappointing and surprising. I really thought that there was going to be a benefit to it."
He struggled to explain the lack of benefit, suggesting that while it is possible the intervention may not work, it's more likely MITRA-FR studied patients whose MR was too far along or included too many operators who were naive to the procedure.
Still, he suggested the MITRA-FR data should give operators pause, at least until COAPT is reported.
"There is widespread use in the world — over 50,000 cases now done for functional MR — and there's no randomized trial benefit, so with all that usage and the first randomized trial being negative, I think everyone should be pausing," Mack said.
Obadia told theheart.org | Medscape Cardiology, "One study is not enough. The problem was that use of the clip was too liberal. Recently, when a patient was in the end stage of heart failure, you don't know what to do, and you put in a clip just because it was safe. This cannot be done now."
"Now I think we have to decrease the number of implantation," he said. "But I prefer not to change the recommendation and leave to the heart team the decision to be more restrictive and to keep the possibility to use the clip in a few highly selected patients and leave confidence in the physician who takes care of the patient."
The study was funded by the French Ministry of Health and Research National Program and by Abbott Vascular, which provided 84% of the clips. Obadia reported having research contracts with Abbott and Neochord and financial relationships with Abbott, Edwards, Medtronic, Landanger, Delacroix Chevalier, and Novartis. Windecker reported receiving research grants from Epic and being involved in studies related to MitraClip.
European Society of Cardiology (ESC) Congress 2018
N Engl J Med. Published online August 27, 2018. Full text
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Cite this: MITRA-FR: MitraClip Comes Up Empty-Handed in Functional Mitral Regurgitation - Medscape - Aug 28, 2018.