The spectacular results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial, presented at TCT 2018, show that transcatheter mitral valve approximation using the MitraClip, on a background of maximally tolerated guideline-directed medical therapy (GDMT) was superior to GDMT alone in the reduction of Heart Failure (HF) hospitalization and mortality in symptomatic HF patients with grade 3-4+ Mitral regurgitation (MR). These landmark findings were simultaneously published today in the New England Journal of Medicine.
Limited treatment options are available for heart failure patients with clinically significant secondary mitral regurgitation (SMR), who continue to be symptomatic despite optimal GDMT and who have been determined by the site’s local heart team as not appropriate for mitral valve surgery. These patients also have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery has not been adequately explored in this population. In the light of this, the goal of the COAPT trial, presented at the 30th annual Transcatheter Cardiovascular Therapeutics (TCT) conference 2018 at San Diego, was to strengthen or add labeling claims regarding the safety and effectiveness of transcatheter MV repair with the MitraClip in symptomatic HF patients with moderate-to-severe or severe SMR.
“In this trial, device-based treatment resulted in a significantly lower rate of hospitalization for heart failure, lower mortality, and better quality of life and functional capacity within 24 months of follow-up than medical therapy alone. In addition, the rate of freedom from device-related complications with transcatheter mitral-valve repair exceeded a prespecified objective performance goal.”- Dr. Gregg W. Stone, M.D.
The COAPT trial was a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with NYHA class II-IVa HF despite treatment with maximally tolerated GDMT who had been determined by the site’s local heart team as not appropriate for MV surgery. The patient population was similar to the MITRA-FR study, presented at the ESC conference, where the results were negative. A total of 614 eligible subjects with HF and grade 3-4+ MR who remained symptomatic despite maximally tolerated GDMT at up to 100 investigational sites were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT in one arm and GDMT alone in the other. The COAPT trial completed patient recruitment in June 2017. The primary effectiveness endpoint was recurrent HF hospitalizations through 24 months, analyzed when the last subject completed 12-months of follow-up, powered to demonstrate the superiority of MitraClip therapy. The primary safety endpoint was a composite of device-related complications at 12 months, compared to a performance goal.
“This trial was very meticulously conducted, including a very carefully selected population. However, effectiveness in the real world will hinge on how closely doctors can replicate the enrolled patient group.”- Dr. Robert W. Yeh, M.D.
The results showed that the primary effectiveness endpoint, which was the annual rate of all hospitalizations for heart failure within 24 months, for MitraClip + GDMT vs. GDMT, was 35.8% vs. 67.9% (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40-0.70, p < 0.001). The primary safety endpoint, which was the rate of freedom from device-related complications at 12 months was 96.6% for MitraClip ( P<0.001). Moreover, the rate of all-cause mortality within 24 months occurred in 29.1% and 46.1% in the device and control groups respectively (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001).
The investigators concluded that transcatheter mitral valve approximation using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality in symptomatic HF patients with grade 3-4+ MR, with excellent safety. Additionally, Stone and his colleagues also noted improvements in LV dimensions and patient symptoms. These exciting findings are bound to have a significant impact on the management of patients with secondary MR. Exercising a word of caution, Dr. Robert Yeh, Director of the Richard and Susan Smith Center for Outcomes Research in Cardiology at the Beth Israel Deaconess Medical Center stated, “This trial was very meticulously conducted, including a very carefully selected population. However, effectiveness in the real world will hinge on how closely doctors can replicate the enrolled patient group.”
“With regard to COAPT, I don’t understand the critics. It would seem that for a breakthrough of such magnitude and beyond any question of statistical significance that can so positively affect hundreds of thousands of suffering patients, the natural human emotion would be to celebrate.”- Dr. Gregg Stone, M.D.