Transcatheter edge-to-edge repair of functional mitral regurgitation in heart failure: Final five-year results from the COAPT Trial

Reported from ACC.23/WCC

Alex Sticchi & Jonathan Curio provide their take on the clinical trial presented by Gregg W. Stone at the American College of Cardiology Scientific Sessions (ACC.23/WCC).

Why this study? – the rationale/objective

Initial results of the COAPT trial, randomizing patients with heart failure and reduced ejection fraction and moderate-to-severe or greater (3+/4+) symptomatic secondary mitral regurgitation (MR) to either mitral transcatheter edge-to-edge repair (M-TEER) with MitraClip (Abbott) or guideline-directed medical therapy alone, were presented in 2018. (1) The strongly positive outcomes of M-TEER after 24-month follow-up, including a marked reduction of heart failure hospitalizations and mortality with a number needed-to-treat of only 6, is reflected by recent ESC/EACTS guidelines. (2) If secondary MR patients meet COAPT trial inclusion criteria, a IIa recommendation for M-TEER is given (and a IIb recommendation to consider M-TEER after careful evaluation of other treatment options if these criteria are not met).

However, longer-term randomized data on treatment effects of M-TEER with MitraClip so far were lacking. Hence, the final 5-year analysis of the COAPT trial evaluated durability of MR reduction achieved by M-TEER and studied its impact on key clinical endpoints.

How was it executed? – the methodology

The COAPT trial enrolled 614 patients with moderate-to-severe (3+) or severe (4+) secondary MR, who remained symptomatic despite optimal GDMT. Patients at baseline suffered from non-ischemic or ischemic cardiomyopathy with an LVEF of 20-50% and were in NYHA class II-IV. Of note, per protocol, 24 months after randomization patients allocated to GDMT were allowed to “crossover” to receive MitraClip treatment.

Primary effectiveness endpoint: cumulative heart failure hospitalizations
Secondary endpoints: death from any cause, MR reduction

What is the main result?

The trial randomized 614 patients to receive M-TEER (n=302) or to receive GDMT only (n=312). Mean age of the patients was 72 years, 43% of M-TEER and 48% of GDMT patients were female. Mean STS-score for risk of surgical mortality was 8% and around 60% were in NYHA class III/IV.

Primary effectiveness endpoint of all HF hospitalizations at 5 years was significantly reduced by M-TEER with MitraClip (HR: 0.53 [0.41-0.68])
All-cause mortality in both groups was high at 5 years (67% in GDMT and 57% in M-TEER group) but was significantly reduced in MitraClip patients (HR: 0.72 [0.58-0.89])
MR reduction was sustained in the device arm with 94.7% at MR ≤ 2+ at 5 years
In patients who crossed over from GDMT to MitraClip after 2 years, outcomes in the first 3 years after treatment were similar to those in patients who received M-TEER at initiation of the study
The procedure was extremely safe with only 4 device-specific events, all occurring during the first 30 days after the procedure, and no further device-specific safety events up to 5 years.

Critical reading and the relevance for clinical practice

These 5-year COAPT results represent the first randomized longer-term data of M-TEER. It is encouraging to see that the positive results from earlier follow-ups regarding heart failure hospitalizations and mortality are maintained up to this longer period of time.

MR reduction by M-TEER using MitraClip appears to be very durable, with over 90% of patients still being in MR ≤ 2+ at 5 years. This favourably compares with experience from surgical repair of MR. The surgical predicate of M-TEER, namely the Alfieri stitch, only showed to be of a durable effect when being combined with mitral annuloplasty, which could have suggested that the mere approximation of the leaflet edges is not sufficient for a durable repair. (3) Importantly, the studied MitraClip represented the first-generation device, while now already an iterated fourth generation is available, adding several features such as different sizes, wider arms, and the ability to individually grasp the leaflets with the two arms of the device – all aspects further enhancing the procedural success, MR reduction, and likely also the durability of the result, including some form of annuloplasty effect by M-TEER.

The endpoints of mortality and heart failure hospitalizations are moving together slightly after 2 years and until 5-year follow-up, however, this is likely also due to a notable number of M-TEER procedures which have been performed in the control group, where 22% received MitraClip after completion of the 24-months follow-up. Of note, these patients who crossed over still experienced benefits from M-TEER in the first three years after the procedure (which is the timespan covered by the trial) similar to the benefit seen in the original device group in their first three years of follow-up.

Still, the very high event rate of heart failure hospitalizations and mortality (to a large extent cardiovascular death driven by ongoing heart failure) highlights the severity of the underlying disease as well as the high disease burden in this particular population. This likely means that: a) patients with heart failure and secondary MR, who are symptomatic despite optimized GDMT and are eligible for M-TEER according to the COAPT inclusion criteria should receive interventional treatment as early as possible, and b) additional studies exploring whether earlier treatment with M-TEER in this patient cohort might improve their prognosis may be needed.

Taken together, these final 5-year results of the COAPT trial provide us with the encouraging message that, in heart failure patients with severe secondary MR, M-TEER with the MitraClip significantly reduces the rate of heart failure hospitalizations and mortality up to 5-years follow-up.

References

Stone GW, Lindenfeld J, Abraham WT et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med 2018.
Vahanian A, Beyersdorf F, Praz F et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2022;43:561-632.
Maisano F, Caldarola A, Blasio A, De Bonis M, La Canna G, Alfieri O. Midterm results of edge-to-edge mitral valve repair without annuloplasty. J Thorac Cardiovasc Surg 2003;126:1987-97.