Key Points:
- Two-year results showed improved outcomes with the MitraClip device but long-term results had not been reported; TEER was allowed in the control arm only after the 2-year primary endpoint assessment.
- At 5 years, the annual rate of hospitalization for HF was 33.1%/year in the device group and 57.2%/year in the control group (HR 0.53; 95% CI 0.41-0.68).
- All- cause mortality through 5 years was lower at 57.3% in the device group and 67.2% in the control group (HR 0.72; 95% CI 0.58-0.89). MitraClip was safe and led to a lower rate of hospitalization for HF and lower all-cause mortality through 5 years of follow-up as compared with medical therapy alone.
Five years after the original COAPT trial was released (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation COAPT; NCT 01626079), we are finally able to discover the long-term results. The COAPT trial made news after the original publication in the New England Journal of Medicine which revealed that at two years there was a significant benefit of MitraClip in patients with all types of cardiomyopathy (defined as left ventricular ejection fraction (LVEF) 20%-50% and LV end-systolic dimension (LVESD) ≤70 mm) and secondary 3-4+ mitral regurgitation (MR) when randomized to MitraClip over guideline directed medical therapy (GDMT) alone, with number needed to treat of 6 patients. To be included in this trial patients also had to have NYHA class II-IVa (ambulatory) HF despite a stable maximally tolerated GDMT regimen and cardiac resynchronization therapy (CRT) (if appropriate). They also had ongoing HF as assessed by ≥1 HF hospitalization within 12 months and/or a B-type natriuretic peptide (BNP) ≥300 pg/ml or a NT-proBNP ≥1500 pg/ml. They were not included if appropriate for mitral valve surgery instead.
COAPT was a multicenter, randomized, parallel-controlled, open-label, that initially included 614 patients, 302 patients were randomized to MitraClip + GDMT and 312 to GDMT alone.. The initial patient population was followed for 5 years. The cliff-hanger at the time of the last results release was that per protocol patients randomized to GDMT were not allowed to “crossover” to the MitraClip arm prior to 24 months, but were permitted to do so after the 2-year mark if they continued to meet the characteristics that made them eligible for the trial.
Presented as a Late Breaking Trial at the 2023 American College of Cardiology Scientific Sessions on Sunday, March 5th, Dr. Gregg W. Stone (Mount Sinai Hospital) on behalf of the COAPT Investigators captivated audiences with the COAPT five-year results. The 5-year trial results were released simultaneously in the New England Journal of Medicine. In total there were 270/302 (89.4%) patients remaining in the MitraClip +GDMT arm and 264/312 (84.6%) in the GDMT alone arm after 5 years. The primary effectiveness endpoint of cumulative HF hospitalizations showed, 33.1%/year were hospitalized in the device group and 57.2%/year in the GDMT alone group (HR [95% CI] = 0.53 [0.41-0.68]). All-cause mortality was similarly higher in the GDMT alone group at 67.2% compared to the MitraClip group with 57.3% at 60 months (HR [95% CI] = 0.72 [0.58-0.89]). Though safety events accumulated over the 60 months with 23 total events in the 293 MitraClip attempted implants, only 4 device-specific events occurred over the entire study period (1.4% in 30 days).
After 2 years, 62 patients originally randomized to the GDMT received MitraClip, with total crossover in 47% of patients. The positive benefits of receiving MitraClip occurred even after this later time point, with a 50% reduction in death or subsequent HF hospitalizations according to multivariable analysis attributed solely to receiving MItraClip in those patients who moved from the GDMT alone arm. Dr. Stone notes, “We did not find that there was a diminishing treatment effect between 3-5 years for HFH and 2-5 years for mortality, which was probably because surviving patients could be treated with MitraClip after 2 years.” Key take-away points therefore include that it is never too late to treat a patient with moderate-severe or severe MR, and that it is ideal to treat patients who remain symptomatic HF patients with severe MR despite optimal medical therapy as early as possible to improve survival. He points out that the caveat is that patients had a high rate of adverse events even after successful mitral valve repair, indicating the need for further advances to treat these high-risk patients.
In an exclusive interview with Cardiology Now News, Dr. Stone states that, “In a sick population of patients with HF and secondary MR, treatment with the MitraClip had a persistent long-term effect of reducing need for HF hospitalizations and improved survival over a 5-year period. Patients felt better, the procedure was extremely safe and there was a durable effect on reducing MR.”
