It remained an open question in 2018, on the unveiling of the COAPT trial’s 2-year primary results, whether the striking reductions in mortality and heart-failure (HF) hospitalization observed for transcatheter edge-to-edge repair (TEER) with the MitraClip (Abbott) would be durable with longer follow-up.
The trial had enrolled an especially sick population of symptomatic patients with mitral regurgitation (MR) secondary to HF.
As it turns out, the therapy’s benefits at 2 years were indeed durable, at least out to 5 years, investigators reported March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The results were simultaneously published in the New England Journal of Medicine.
Patients who received the MitraClip on top of intensive medical therapy, compared with a group assigned to medical management alone, benefited significantly at 5 years with risk reductions of 51% for HF hospitalization, 28% for death from any cause, and 47% for the composite of the two events.
Still, mortality at 5 years among the 614 randomized patients was steep at 57.3% in the MitraClip group and 67.2% for those assigned to meds only, underscoring the need for early identification of patients appropriate for the device therapy, Gregg W. Stone, MD, said during his presentation.
Dr. Stone, of the Icahn School of Medicine at Mount Sinai, New York, is a COAPT co-principal investigator and lead author of the 5-year outcomes publication.
Outcomes were consistent across all prespecified patient subgroups, including by age, sex, MR, left ventricular (LV) function and volume, cardiomyopathy etiology, and degree of surgical risk, the researchers reported.
Symptom status, as measured by New York Heart Association (NYHA) functional class, improved throughout the 5-year follow-up for patients assigned to the MitraClip group, compared with the control group, and the intervention group was significantly more likely to be in NYHA class 1 or 2, the authors noted.
The relative benefits in terms of clinical outcomes of MitraClip therapy narrowed after 2-3 years, Dr. Stone said, primarily because at 2 years, patients who had been assigned to meds only were eligible to undergo TEER. Indeed, he noted, 45% of the 138 patients in the control group who were eligible for TEER at 2 years “crossed over” to receive a MitraClip. Those patients benefited despite their delay in undergoing the procedure, he observed.
Dr. Gregg W. Stone
However, nearly half of the control patients died before becoming eligible for crossover at 2 years. “We have to identify the appropriate patients for treatment and treat them early because the mortality is very high in this population,” Dr. Stone said.
“We need to do more because the MitraClip doesn’t do anything directly to the underlying left ventricular dysfunction, which is the cause of the patient’s disease,” he said. “We need advanced therapies to address the underlying left ventricular dysfunction” in this high-risk population.
Exclusions based on LV dimension
The COAPT trial included 614 patients with HF and symptomatic MR despite guideline-directed medical therapy. They were required to have moderate to severe (3+) or severe (4+) MR confirmed by an echocardiographic core laboratory and a left ventricular ejection fraction (LVEF) of 20%-50%.
Among the exclusion criteria were an LV end-systolic diameter greater than 70 mm, severe pulmonary hypertension, and moderate to severe symptomatic right ventricular failure.
The systolic LV dimension exclusion helped address the persistent question of whether “severe mitral regurgitation is a marker of a bad left ventricle or ... contributes to the pathophysiology” of MR and its poor outcomes, Dr. Stone said.
The 51% reduction in risk for time-to-first HF hospitalization among patients assigned to TEER “accrued very early,” Dr. Stone pointed out. “You can see the curves start to separate almost immediately after you reduce left atrial pressure and volume overload with the MitraClip.”
The curves stopped diverging after about 3 years because of crossover from the control group, he said. Still, “we had shown a substantial absolute 17% reduction in mortality at 2 years” with MitraClip. “That has continued out to 5 years, with a statistically significant 28% relative reduction,” he continued, and the absolute risk reduction reaching 10%.
Patients in the control group who crossed over “basically assumed the death and heart failure hospitalization rate of the MitraClip group,” Dr. Stone said. That wasn’t surprising “because most of the patients enrolled in the trial originally had chronic heart failure.” It’s “confirmation of the principal results of the trial.”
Comparison With MITRA-FR
“We know that MITRA-FR was a negative trial,” observed Wayne B. Batchelor, MD, an invited discussant following Dr. Stone’s presentation, referring to an earlier similar trial that showed no advantage for MitraClip. Compared with MITRA-FR, COAPT “has created an entirely different story.”
The marked reductions in mortality and risk for adverse events and low number-needed-to-treat with MitraClip are “really remarkable,” said Dr. Batchelor, who is with the Inova Heart and Vascular Institute, Falls Church, Va.
But the high absolute mortality for patients in the COAPT control group “speaks volumes to me and tells us that we’ve got to identify our patients well early,” he agreed, and to “implement transcatheter edge-to-edge therapy in properly selected patients on guideline-directed medical therapy in order to avoid that.”
The trial findings “suggest that we’re reducing HF hospitalization,” he said, “so this is an extremely potent therapy, potentially.
“The dramatic difference between the treated arm and the medical therapy arm in this trial makes me feel that this therapy is here to stay,” Dr. Batchelor concluded. “We just have to figure out how to deploy it properly in the right patients.”
The COAPT trial presents “a practice-changing paradigm,” said Suzanne J. Baron, MD, of Lahey Hospital & Medical Center, Burlington, Mass., another invited discussant.
The crossover data “really jumped out,” she added. “Waiting to treat patients with TEER may be harmful, so if we’re going to consider treating earlier, how do we identify the right patient?” Dr. Baron asked, especially given the negative MITRA-FR results.
MITRA-FR didn’t follow patients beyond 2 years, Dr. Stone noted. Still, “we do think that the main difference was that COAPT enrolled a patient population with more severe MR and slightly less LV dysfunction, at least in terms of the LV not being as dilated, so they didn’t have end-stage LV disease. Whereas in MITRA-FR, more of the patients had only moderate mitral regurgitation.” And big dilated left ventricles “are less likely to benefit.”
There were also differences between the studies in technique and background medical therapies, he added.
The Food and Drug Administration has approved – and payers are paying – for the treatment of patients who meet the COAPT criteria, “in whom we can be very confident they have a benefit,” Dr. Stone said.
“The real question is: Where are the edges where we should consider this? LVEF slightly less than 20% or slightly greater than 50%? Or primary atrial functional mitral regurgitation? There are registry data to suggest that they would benefit,” he said, but “we need more data.”
COAPT was supported by Abbott. Dr. Stone disclosed receiving speaker honoraria from Abbott and consulting fees or equity from Neovasc, Ancora, Valfix, and Cardiac Success; and that Mount Sinai receives research funding from Abbott. Disclosures for the other authors are available at nejm.org. Dr. Batchelor has disclosed receiving consultant fees or honoraria from Abbott, Boston Scientific, Idorsia, and V-Wave Medical, and having other ties with Medtronic. Dr. Baron has disclosed receiving consultant fees or honoraria from Abiomed, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, Shockwave, and Zoll Medical, and conducting research or receiving research grants from Abiomed and Boston Scientific.
A version of this article originally appeared on Medscape.com.