SAN DIEGO — MitraClip plus maximally-tolerated guideline-directed medical therapy (GDMT) proved to be a significantly more effective treatment for patients with heart failure (HF) and moderate to severe secondary mitral regurgitation (MR) compared to GDMT alone, according to results of the highly anticipated COAPT trial released Sunday at the Transcatheter Cardiovascular Therapeutics (TCT) conference.
“I just think that this is a landmark trial that’s going to change public practice,“ said Martin B. Leon, MD, whose institution, Columbia University Medical Center in New York, was part of the trial, although he did not perform any of the procedures.
COAPT included 614 patients at 78 centers in the US and Canada with HF and moderate to severe MR who remained symptomatic despite maximally-tolerated GDMT. The patients were randomized to treatment with MitraClip (Abbott Vascular) plus GDMT or GDMT alone.
The primary safety endpoint was freedom from device-related complications at 12 months. The primary effectiveness endpoint was recurrent HF hospitalizations through 24 months, which was analyzed when the last patient completed 12-month follow-up.
Patients with MitraClip outperformed those on medical therapy alone with regard to the primary effectiveness endpoint. The GDMT-only group had 283 HF hospitalizations in 151 patients, which Gregg W. Stone, MD, of the Cardiovascular Research Foundation in New York, said was significantly lower, 160 HF hospitalizations in 92 patients, in the MitraClip group.
Stone, principal investigator of the trial, said that translates to 67.9% of GDMT-only patients being hospitalized for HF per year compared to only 35.8% of MitraClip patients (HR 0.53 [95% CI 0.40-0.70], p<0.001). Also, the number of patients needed to treat with MitraClip to prevent 1 HF hospitalization in 2 years was 3.1 [95% CI 1.9-8.2].
Turning to the primary safety endpoint, 96.6% of MitraClip patients were free from device-related complications at 12 months. This was defined as a composite of single leaflet device attachment, device embolization, endocarditis requiring surgery, mitral stenosis requiring surgery, left ventricular assist device implantation, heart transplant, or any device-related complication requiring non-elective cardiovascular surgery.
The high rate of freedom from device-related complications, Stone said, easily surpassed the objective performance goal criterion of 88%.
The trial was also powered to measure 10 secondary endpoints tested in hierarchical order to control for multiplicity. Nine of these endpoints were powered for superiority; the other, all-cause mortality at 12 months, was powered for noninferiority. MitraClip met all 10 of the secondary endpoints, which included reduction of mitral regurgitation grade at 12 months, death and all heart failure hospitalization through 24 months, and change in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire.
Stone singled out all-cause mortality as one of the more important endpoints. In the MitraClip group, 29.1% of patients had died by 2-year follow-up, compared to 46.1% of GDMT patients (HR 0.62 [95% CI 0.46-0.82], p<0.001), saving 17 lives per 100 patients treated. The number of patients needed to treat with MitraClip to save 1 life in 2 years was 5.9 [95% CI 3.9-11.7].
These results stand in sharp contrast to those of the MITRA-FR trial, released in August at the European Society of Cardiology Congress,
MITRA-FR randomized 307 patients with HF and secondary MR at 37 centers in France to receive MitraClip plus medical therapy or medical therapy alone.
Stone pointed out three major reasons for the different results of the two trials.
First, COAPT patients had more severe MR than did the MITRA-FR patients. COAPT patients had a mean effective regurgitant orifice area of 41±15 mm2 compared to 31±10 mm2 in MITRA-FR. Also, the COAPT patients’ ventricles were not severely dilated (101±34 mL/mm2), whereas the dilation was greater in MITRA-FR patients (135±35 mL/mm2). The less-severe MR and more-dilated ventricles might account for the lack of impact by MitraClip in MITRA-FR, Stone said.
Second, in MITRA-FR, the HF medications were allowed in both groups of patients to vary as per real-world practice. Stone suggested that, while there are not data to show this currently, it is possible in MITRA-FR that patients in the control group were treated more aggressively. By contrast, in COAPT, enrolled patients were confirmed to be on maximally-tolerated GDMT, and there were few major changes in HF medications in both groups throughout the trial.
Finally, there were fewer procedural complications in COAPT (8.5%) than in MITRA-FR (14.6%) and greater durability in COAPT (MitraClip patients with increase in MR of 3 or more levels, 5% in COAPT, 17% in MITRA-FR). Stone said this suggests “perhaps greater experience in the COAPT operators.”
Stone concluded his presentation by saying that in patients with HR and moderate to severe secondary MR who remained symptomatic despite maximally-tolerated GDMT, transcatheter mitral leaflet approximation with the MitraClip was safe, provided durable reduction in MR, reduced the rate of HF hospitalizations, and improved survival, quality of life and functional capacity at 2-year follow-up.
“As such, the MitraClip is the first therapy shown to improve the prognosis of patients with heart failure by reducing secondary MR due to left ventricular dysfunction,” he said.
The panelists did caution that the results may not be generalizable to real-world practice, primarily because of the difficulty of providing optimal medical therapy outside of clinical trials.
“It’s well-known in the field of heart failure that device therapy is more effective when you’re on optimal guideline-directed medical therapy,” said Michael J. Mack, MD, of Baylor Scott and White Heart Hospital Plano, Texas, co-principal investigator of the trial. “So the message for the community is going to be, if MitraClip is going to be effective, these patients have to be treated with guideline-directed medical therapy.”
Both MITRA-FR and COAPT received funding support from Abbott Vascular. MITRA-FR was sponsored by Hospices Civil de Lyon, France, and COAPT was sponsored by Abbott.