Percutaneous Mitral Repair Looks Durable, Safe, in 5-Year Final Results from EVEREST II

Although patients with mitral regurgitation (MR) who are treated with percutaneous repair are more likely than those who receive surgery to require a second procedure in the first year, long-term follow up shows that the device is both safe and durable with comparable rates of repeat procedures in later years, according to final results of the EVEREST II trial. However, questions and criticisms remain around some of the key inclusion criteria and the choice of primary endpoint. 

Five-year results were published in the December 29, 2015 issue of the Journal of the American College of Cardiology.

Speaking about the 5-year results, Ted Feldman, MD, of NorthShore University HealthSystem (Evanston, Illinois), told TCTMD that the main message is that out to 5 years, all major outcomes for surgery and Mitraclip are virtually identical. 

“The surprise is that our colleagues in the surgery world had predicted that without an annuloplasty, Mitraclip would not be durable, but here were are at 5 years. Between 1 and 5 years, the existing baseline residual MR hasn’t gotten worse and interestingly, the septal-lateral dimensions have been completely stable,” he said.

EVEREST II randomized 279 asymptomatic or symptomatic patients with moderate to severe (grade 3+ or 4+) MR to percutaneous treatment with the MitraClip system (Abbott Vascular; Santa Clara, CA; n = 184) or surgical repair or replacement (n = 95).

Patients were enrolled at 37 study centers in North America between September 2005 and November 2008. Mean age was 67 years in the percutaneous group and 64.7 years in the surgery group, with women accounting for 36.5% and 33.8%, respectively. Functional MR was present in 27% of the percutaneous group and 22.5% of the surgery group, while mean LVEF was 59.9% and 61.3%, respectively.

Single leaflet device detachment occurred in 9 patients in the first year, with 1 additional patient experiencing late detachment at approximately 14 months. All patients with detachment underwent MV surgery (5 replacement, 5 repair).

The 5-year follow up included 154 patients from the device arm and 56 from the surgical arm. The rate of the composite efficacy endpoint (freedom from death, MV surgery, or 3+ or 4+ MR) in the as-treated population was lower in the percutaneous group, with no differences in the individual endpoint of mortality between the 2 groups. However, need for surgery or reoperation and 3+ or 4+ MR both were more frequent with percutaneous repair. 

As has been reported in prior follow ups from EVEREST II, an early hazard for MV surgery emerged in the percutaneous group in the first year of follow up, with 78% of those surgeries occurring within 6 months. However, from 6 months through 5 years, no difference was seen in the rate of freedom from surgery for MV dysfunction between the percutanous and surgery groups (P = .77).

Both groups had substantial reductions in MR from baseline to 12 months, and from baseline to 5 years. Despite this, patients in the surgery group were much more likely than those in the percutaneous group to have frequent NYHA functional class III/IV symptoms at 12 months with  (7.5% vs 1.0%; P = .03). At 5 years, the trend unexpectedly reversed, with more percutaneous patients having frequent symptoms, but the difference was not significant (P = .19). 

In multivariable analyses, functional MR, COPD, older age, diabetes, and PAD were all independent predictors of 5-year mortality.

“The results in the Mitraclip group have held up and there has not been any evidence of annular dilatation or progressive MR,” Feldman noted, adding that the EVEREST II experience shows that the procedure can be done with “remarkable relative safety” and that if a good acute result is achieved “there is expectation of durability for several years.”

Criticisms Too, Remain at 5 Years

In an editorial accompanying the study, Anelechi C. Anyanwu, MD, and David H. Adams, MD, both of Mount Sinai Medical Center (New York, NY), note that while EVEREST II was “pioneering,” several important lessons have been gleaned from the trial that “can help form the framework for future trials of transcatheter mitral valve therapy.” Chief among the criticisms that have been raised about the trial over the years is the fact that it enrolled both degenerative MR and functional MR patients, which “greatly limited interpretation and applicability of the results,” they observe.

Feldman maintained that Kaplan-Meier snapshots of the 5-year outcomes by etiology show that the curves for degenerative and functional patients overlap with surgery. “We all wish that we had a huge trial with a zillion patients of each etiology,” Feldman said, “But for what we have, the results are remarkably consistent.”

Additionally, about one-third of patients who had failed device placement did not undergo subsequent surgery during the initial study period, Anyanwu and Adams say, “raising the question as to how strong an indication for surgery had existed in those patients in the first place,” and making it difficult to extrapolate the results, since the possibility exists that Mitraclip was used in less-severe stages of disease.

Furthermore, they question the inclusion of death in the effectiveness endpoint for mitral repair devices because repair is not typically performed to enhance short-term survival.

“In a strict sense, death should be part of a safety endpoint, as should other major adverse major clinical events,” they write.

“I have to disagree pretty strongly that if you can’t look at death and reoperation together as a long-term outcome you don’t get a clear picture at all of how these patients do,” Feldman countered.

Finally, the editorialists question the EVEREST II investigators’ inclusion of patients who were candidates for mitral repair or replacement, noting that Mitraclip is a repair device and should be used as an alternative to surgical repair and not surgical replacement.

“Future trials of percutaneous or surgical repair devices should pre-specify surgical repairability as an inclusion criteria, and any valve replacement (surgical or percutaneous) should be seen as a failure,” they conclude. 

Sources: 
1. Feldman T, Kar S, Elmariah S, et al. Randomized comparison of percutaneous repair and surgery for mitral regurgitation 5-year results of EVEREST II. J Am Coll Cardiol. 2015;66:2844-2854.
2. Anyanwu AC, Adams DH. Evaluating catheter-based mitral valve therapies: lessons learned and future directions. J Am Coll Cardiol. 2015;66:2855-2859. 

Disclosures:

• Feldman reports serving as a consultant for and receiving honoraria/institutional research support from Abbott Vascular, Boston Scientific, Edwards, and WL Gore. 
• Anyanwu reports no relevant conflicts of interest. 
• Adams reports serving as the national co-principal investigator of the Medtronic CoreValve US Pivotal Trial and that his institution receives royalties related to intellectual property for valve repair devices from Edwards Lifesciences and Medtronic. 

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• EVEREST II Registry Looks at MitraClip in High-Risk Patients