EVEREST II: Two-Year Outcomes Show Positive, Negative Aspects of MitraClip

NEW ORLEANS, LA—Two-year results from the EVEREST II clinical trial show that percutaneous mitral valve repair with the MitraClip device is a durable option for patients with moderate to severe mitral regurgitation (MR), but offers less effective MR reduction compared with surgical treatment. At 2 years, 1 in 5 percutaneously-treated patients required surgical valve repair or replacement, with most needing surgery in the 6 months following insertion of the clip.

The 2-year findings were presented in a late-breaking clinical trial session at the annual American College of Cardiology Scientific Session/i2 Summit on April 4, 2011. The 1- and 2-year results were simultaneously published in the New England Journal of Medicine.

In the EVEREST II trial, 279 patients with moderate-to-severe or severe MR (3+ or 4+) and anatomical criteria suitable for endovascular repair were randomly assigned (2:1) to percutaneous treatment with the MitraClip system (n = 184) or surgical repair or replacement (n = 95). The MitraClip system (Evalve, Inc, Menlo Park, CA) involves a clip that is inserted into the mitral valve via percutaneous femoral venous transseptal access. The device is then aligned above the valve in order to secure the mitral leaflets.

One- and two-year findings indicated similar rates of death with the MitraClip device compared to surgery and similar MR reduction, with about 20% of all patients still having 3+ or 4+ MR. However, the primary efficacy endpoint of freedom from death, MV surgery or re-operation, or 3+ or 4+ MR favored surgery, driven primarily by a significantly higher rate of surgical intervention in the percutaneous group (table 1).

Table 1. Two-Year Outcomes, Intention-to-Treat Analysis           

 

Percutaneous
(
n = 172)

Surgery
(n = 83)

P Value

Primary Endpointa

51.7%

66.3%

< 0.001

Death

11.0%

10.8%

> 0.999

MV Surgery/Re-operation

22.1%

3.6%

< 0.001

3+ or 4+ MR

19.8%

21.7%

0.84

Abbreviation: MR, mitral regurgitation.

aFreedom from death, MV surgery/re-operation, 3+ or 4+ MR.

In a secondary “treatment strategy comparison” analysis, wherein mitral valve surgery following unsuccessful percutaneous repair was not considered an endpoint event, equivalence between the 2 treatment options was demonstrated (P = 0.67).

Dr. Feldman noted that most of the need for surgical intervention after percutaneous repair occurred in the first 6 months, resulting in similar rates of freedom from surgical intervention in the percutaneous arm at 1 and 2 years (78.8% and 78.2%, respectively). He also mentioned that the procedural success rate in the trial was 85%, but has since risen to 95% or 96% in the post-randomization registry, hinting that with more experience with the clip, subsequent surgeries might be avoided.

Device Proves Safe, Durable

As opposed to the primary efficacy endpoint, the MitraClip met its primary safety endpoint as previously shown, with a significantly lower rate of major adverse events at 30 days compared to surgery (15% vs. 48%; P < 0.001).

The device has also shown itself to be durable. At 2 years, no percutaneous device embolization, fracture, erosion, or migration was noted. The 1-year leaflet device attachment rate was 6.3%, with no additional reports of single leaflet device attachment seen between 1 and 2 years.

Both percutaneous and surgical treatment reduced MR severity and significantly improved left ventricular volumes and NYHA functional class.

Explaining the rationale behind the 2 different analyses (intention-to-treat vs. treatment strategy comparison), Dr. Feldman said: “The intention-to-treat analysis tells the patients: What are the odds when you walk in at the end of the year that the clip will be successful and you’ll be doing okay? And the answer to that question is, 78% of patients were free from the need for surgery at 2 years and 97% of them had NYHA functional class I or II symptoms.

“The second question the patient asks is: What if I am in that 20% that needs surgery? The second analysis didn’t exclude surgery, but rather than counting surgery as a failure, it counted the combined strategy of clip or clip with surgery, if needed, as successful therapy for the disease,” he added.

Half Full or Half Empty?

Commenting on the trial, cardiothoracic surgeon, Steven F. Bolling, MD, of the University of Michigan Medical School (Ann Arbor, MI) said that, “clearly, the MitraClip will become a useful tool in selected subpopulations of patients with mitral regurgitation.” He noted that the trial enrolled both patients with degenerative leaflet disease (75%) and functional MR (25%), which are “very different subsets.”

“These patients with functional, or dilated cardiomyopathy-associated mitral regurgitation are high-risk patients and are probably actually a very good subset to study for the MitraClip and I think further follow-up in that group will tell us where this very useful tool will end up,” Dr. Bolling added.

To this, Dr. Feldman replied that current referral patterns favor patients with high-risk, predominantly functional MR and that outcomes in these higher-risk individuals “are virtually identical to what we see in the randomized trial.”

In an editorial accompanying the publication of the EVEREST II results, Catherine M. Otto, MD, and Edward D. Verrier, MD, both of the University of Washington School of Medicine (Seattle, WA), express some disappointment over the amount of residual 2+ MR seen in the MitraClip arm of the study (46% vs. 17% in the surgical group at 12 months). "This modest reduction in regurgitant severity might be associated with favorable short-term and midterm outcomes, but surgical series suggest that residual mitral regurgitation predicts adverse long-term clinical outcomes,” they wrote.

Dr. Bolling mentioned that some of the more contemporary MitraClip recipients are actually receiving 2 clips, which might be more effective in eliminating residual regurgitation.

 

Sources:

  1. Feldman T, Foster R, Glower DG, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011;Epub ahead of print.
  2. Otto CM, Verrier ED. Mitral regurgitation—What is best for my patient? N Engl J Med. 2011;Epub ahead of print.

Related Stories:

Disclosures
  • The EVEREST II trial was supported by Abbott Vascular.
  • Dr. Feldman reports receiving research grants from and serving as a consultant to Abbott and Edwards.

We Recommend

Comments