The largest real-world prospective outcome study to date, including 5,000 consecutive heart failure (HF) patients with secondary mitral regurgitation (SMR), reinforces the safety and effectiveness of transcutaneous edge-to-edge repair (TEER) using the MitraClip System (Abbott).

These data were published by Kashish Goel, MD, from the Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues in a manuscript published Monday online and in the Sept. 26 issue of the Journal of the American College of Cardiology.

The two pivotal randomized controlled trials (RCTs) of the MitraClip device in HF patients with SMR – The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) and the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) came up with conflicting results. While the COAPT trial showed a significant reduction in mortality and heart failure hospitalization with TEER and guideline-directed medical therapy (GDMT) versus GDMT alone, the MITRA-FR trial did not show any benefit of TEER compared with GDMT. This discrepancy resulted in several hypotheses, mainly focused on patient selection and variability in the reduction of mitral regurgitation (MR) between the two studies.

This COAPT post-approval study (COAPT-PAS) evaluated the safety and efficacy of the MitraClip in a real-world population. This is a contemporary study in which 98% of patients were treated with third- and fourth-generation devices, compared to first-generation systems in the RCTs. The authors also included a secondary analysis to identify the subset of patients in the COAPT-PAS who met the inclusion and exclusion criteria for the COAPT (COAPT-like) and MITRA-FR (MITRA-FR-like) and examined their outcome.

Study details

This prospective, single-arm, multicenter, observational, real-world surveillance study was done using the Transcatheter Valve Therapy (TVT) Registry. It includes 5,000 consecutive patients from 406 commercial centers in the United States from March 2019 to September 2020.

The patients in COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less GDMT than those in the COAPT or MITRA-FR studies. Despite that, the implantation rate was excellent (97.7%), and the reduction of MR to £2 at 1 year was comparable between the COAPT-PAS and the RCTs (90.7%, compared with 89.7% and 86.6% in the COAPT and MITRA-FR, respectively). Also, the procedure proved safe with a low rate of adverse events at 1 year, comparable to the RCT. This provides reassurance regarding the safety of the procedure even in less selective, sicker real-world populations (only ~20% of the COAPT-PAS population would have been eligible for the RCTs).

As for the clinical outcomes, the combined rate of all-cause mortality and/or HF hospitalizations (HFH) at 1-year in the COAPT-PAS full cohort (33.7%) was comparable to the TEER+GDMT arm of the COAPT study (33.5%; p=0.80), and significantly lower than the COAPT study GDMT arm (46.2%; p<0.0001). This finding was driven by a lower rate of HFH (18.9%), which was lower than both the COAPT study TEER+GMDT group (24.9%; p=0.02) and the COAPT study GMDT group (39.6%; p<0.0001). One-year mortality was similar between the groups.

The results were similar in the secondary analysis for the COAPT-like patients but with a statistically lower rate of 1-year mortality in the COAPT-PAS COAPT-like subgroup as compared with the COAPT-RCT GDMT arm (17% vs. 23.1%; p=0.02). For the MITRA-FR COAPT-like group, the 1-year mortality and/or HFH composite was lower compared with the MITRA-FR-RCT TEER+GDMT group and the GDMT arm (43.6% versus 51.3% and 54.6%, respectively). This was mainly driven by a reduced rate of HFH. Also, a large improvement in quality of life in 1 year was found (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like and +33 MITRA-FR-like).

Editorial comment and evaluation

An editorial comment was published simultaneously by Mathias Orban, MD, and Jörg Hausleiter, MD, from the Hospital of the University of Munich. They emphasized that the real-world study better represents the patient population clinicians encounter.

“The COAPT/MITRA-FR trial patients are clearly a minority in the real-world spectrum of patients with severe SMR,” wrote Orban and Hausleiter, who is also with the German Center for Cardiovascular Research in Munich. “Patients in COAPT-PAS, among other parameters, more frequently had severe tricuspid regurgitation (TR), had more challenging mitral valve anatomies (for example, leaflet calcification), had more comorbidities, and were more often female as compared to both RCTs.”

When analyzing the results, they stated: “The main benefit of M-TEER in COAPT-PAS patients was evidenced by low heart failure hospitalization (HFH) rates at the 1-year follow-up (FU). The differences in 1-year all-cause mortality were small, which might be explained by the relatively short and incomplete 1-year FU. (The FU rate in COAPT-PAS was only 53%.) Accordingly, it will be interesting to see if a longer and complete FU of the real-world COAPT-PAS study population will show differences in mortality compared to the original COAPT and MITRA-FR study populations.”

They concluded that “the results of COAPT-PAS and other real-world registries have unambiguously shown that: 1) M-TEER is safe; 2) M-TEER effectively reduces MR; and 3) M-TEER is associated with improved outcomes outside of randomized trials.”

They that “transcatheter edge-to-edge therapy for SMR is now a guideline-recommended therapeutic option for heart failure patients with SMR, but many more questions remain to be answered to accompany the successful expansion of M-TEER in real-world daily practice and to further optimize outcomes in this vulnerable patient population.”

Sources:

Goel K, Lindenfeld J, Makkar R, et al. Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study. J Am Coll Cardiol 2023;82:1281–1297.

Orban M, Hausleiter J. Expanding Success of Mitral Transcatheter Edge-to-Edge Repair in Real-World Patients: And More Questions to Answer. J Am Coll Cardiol 2023;82:1298–1300.

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