Last month, Abbott announced US Food and Drug Administration (FDA) approval of a new trial—REPAIR MR—to evaluate the safety and efficacy of percutaneous edge-to-edge repair (MitraClip) for the management of patients with primary mitral regurgitation at moderate surgical risk. MitraClip currently has market approval in both Europe and the USA for the management of primary and secondary mitral regurgitation in patients at high surgical risk. Coprincipal investigator of the study Patrick M McCarthy (Northwestern Medicine Bluhm Cardiovascular Institute, Chicago, USA) talks to Cardiovascular News about the rationale for the trial.
What proportion of primary mitral regurgitation patients who are eligible for surgery actually undergo open mitral valve repair/replacement?
Approximately 70% of people diagnosed with primary mitral regurgitation do not receive treatment. However, knowing the exact percentages at this point in time is difficult because of this under treatment—in some cases, this is because mitral regurgitation is very difficult to diagnose and may be missed.
Why do so relatively few surgical candidates undergo open mitral repair/replacement?
Mitral valve disease continues to be undertreated and only a limited number of patients undergo mitral surgery, even when surgical options are available. This may be because the mitral regurgitation has not been diagnosed or because the patient does not want to undergo a surgical procedure.
What existing data are available for the use of MitraClip for the management of primary mitral regurgitation in patients who are surgical candidates?
The long-term outcomes for MitraClip have been well documented, particularly from the EVEREST II and REALISM trials.
[EVEREST II investigators (Feldman et al) reported in the Journal of American College of Cardiology in 2015 that patients treated with MitraClip more frequently required surgery for residual mitral regurgitation during the first year after treatment compared with those who underwent surgery. However, they also found that, between one- and five-year follow-up, both percutaneous repair (with MitraClip) and surgical repair were associated with comparably low rates of surgery for mitral valve dysfunction, which the authors said endorsed “the durability of mitral regurgitation reduction with both repair techniques”.]
What are the aims of REPAIR-MR?
We will evaluate the effect of repair with MitraClip versus that of repair with mitral valve surgery, looking at long-term clinical outcomes in a patient population primarily aged 75 or older that is considered to be at moderate surgical risk for surgery. There are limitations to open heart surgery in this population.
Advanced age has consistently been shown to be a risk factor for operative mortality with mitral valve surgery. Although the patient population of this trial is at a lower risk compared to the high risk indication, these patients remain at increased risk of morbidity and mortality with conventional surgery versus patients at low surgical risk.
What will REPAIR MR need to show for Abbott to get an FDA-approved indication for MitraClip to be used in moderate-surgical patients?
Any potential indication granted by the FDA is expected to be driven by the trial’s inclusion/exclusion criteria, the patient population enrolled, and the trial’s outcomes.
Do you think there is any scope for MitraClip to provide superior outcomes in this cohort?
Long-term outcomes with contemporary MitraClip devices and with mitral valve surgical repair in an elderly patient population at moderate surgical risk are not known. For this reason, REPAIR MR is an important trial and will provide clinical outcomes data in this patient population for the first time.