Transcatheter mitral valve repair significantly reduces hospitalization and all-cause mortality compared with medical therapy alone in patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remain symptomatic despite optimal medical therapy.
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So indicate two-year results from the multicenter COAPT trial, which were reported in a late-breaking presentation at the 2018 Transcatheter Cardiovascular Therapeutics conference (TCT 2018) in late September and simultaneously published online in the New England Journal of Medicine.
“This study is likely to change the management of this high-risk patient population with symptomatic mitral regurgitation secondary to heart failure,” says Cleveland Clinic’s Samir Kapadia, MD, one of the COAPT trial’s lead investigators and a member of its steering committee.
“These findings mean that we have an important new option for patients with heart failure and severe functional mitral regurgitation,” adds Cleveland Clinic Cardiothoracic Surgery Chair A. Marc Gillinov, MD, who served on advisory and central eligibility committees for the COAPT trial. “Most of these patients are not good surgical candidates, but they can now receive a mitral procedure that improves their prognosis.”
COAPT’s more-robust-than-expected findings are likely to lead to FDA approval of the trial’s transcatheter mitral valve repair device, the MitraClip® (shown in photo at top), for a new indication — treatment of secondary mitral regurgitation. The device was approved by the FDA in 2013 for treatment of primary mitral regurgitation in patients at prohibitive risk from surgery. Outside the U.S., however, MitraClip has been used most widely to treat secondary mitral regurgitation in patients with heart failure. That use has been based on uncontrolled registry studies.
“Treatment of secondary mitral regurgitation in heart failure patients has never been shown to be beneficial in reducing mortality,” explains Dr. Kapadia, Section Head of Invasive and Interventional Cardiology at Cleveland Clinic. “We undertook COAPT to more definitively evaluate the potential utility of MitraClip in this population relative to optimal medical therapy.”
Design and key results
Cleveland Clinic was one of 78 North American sites enrolling patients in COAPT. All enrollees had heart failure and moderate-to-severe or severe secondary mitral regurgitation and were symptomatic despite maximal doses of guideline-directed medical therapy. Patients were randomized to transcatheter mitral valve repair plus medical therapy (device group; n = 302) or to medical therapy alone (control group; n = 312).
On the study’s primary effectiveness end point — annualized hospitalization rate for heart failure within 24 months — the device group had a significantly better rate than the control group: 35.8 percent vs. 67.9 percent per patient-year (hazard ratio [HR] = 0.53, 95% CI, 0.40 to 0.70; P < .001).
The primary safety end point was freedom from device-related complications at 12 months, with 88.0 percent designated as the prespecified objective performance goal. The actual rate of freedom from device-related complications was found to be 96.6 percent — significantly superior to the performance goal (P < .001). “This confirmed incredible safety of this percutaneous procedure,” notes Dr. Kapadia.
Additional findings, impressive NNT data
Among other key findings:
- Death from any cause at 24 months was significantly less common in the device group (29.1 percent) than in the control group (46.1 percent) (HR = 0.62, 95% CI, 0.46 to 0.82; P < .001).
- Mean change in the Kansas City Cardiomyopathy Questionnaire score, a quality-of-life measure, was significantly greater in the device group than in the control group (12.5 ± 1.8 points vs. –3.6 ± 1.9 points; P < .001) (higher scores are better).
- The benefits of device therapy were consistent across multiple subgroups (including those with ischemic and nonischemic cardiomyopathy) and were independent of mitral regurgitation grade and left ventricular volume and function at baseline.
- The lower rate of heart failure-related hospitalization in the device group was evident within 30 days after treatment, whereas the mortality benefit emerged more than a year after treatment. Dr. Kapadia notes that this delayed response in terms of mortality is in keeping with long-term benefits from a durable reduction in the severity of left ventricular volume overload.
He adds that the most striking results may be the study’s number-needed-to-treat data: “We found that we need to treat just three patients to prevent one hospitalization and treat six patients to save a life! This is one of the most beneficial treatment results we have ever observed in a clinical trial.”
What about MITRA-FR?
These findings of robust benefit with transcatheter mitral valve repair in COAPT are in contrast to results of the earlier and smaller MITRA-FR study among a similar patient population in France. That study found that MitraClip did not improve the 12-month rate of all-cause mortality and heart failure hospitalization compared with medical therapy alone.
Dr. Kapadia observes that beyond differences in size — COAPT had twice as many patients at MITRA-FR — the studies differed in other ways that could explain their varying findings. “Patients’ medications were not optimized as well in MITRA-FR as in COAPT, and operators in the MITRA-FR study were not as experienced as COAPT investigators,” he says. “Additionally, MITRA-FR patients had larger left ventricular size and less severe mitral regurgitation compared with COAPT patients,” as COAPT used the more strict U.S. criteria for mitral regurgitation severity.
“The COAPT trial demonstrates that transcatheter mitral valve repair is a safe intervention that confers reductions in hospitalization and death in patients with moderate-to-severe and severe mitral regurgitation secondary to heart failure,” Dr. Kapadia says. “These are patients without good treatment options, so this is a very welcome development.”
He predicts the findings could substantially expand the use of MitraClip, although appropriate patient selection will be key. “There are several new percutaneous therapies being developed and tested in clinical trials,” he notes. “Patients may benefit from evaluation in experienced centers where all these options are available.”