EVEREST II Registry Looks at MitraClip in High-Risk Patients

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A registry analysis from the EVEREST II study cohort shows that percutaneous repair of mitral regurgitation (MR) in high-risk patients reduces MR and improves clinical symptoms, according to results published in the January 10, 2012, issue of the Journal of the American College of Cardiology. But outside experts cautioned that due to a number of limitations in the study, the results, though positive, should only be viewed as providing impetus for a more definitive trial.

EVEREST II randomized 279 patients with moderate-to-severe or severe MR (3+ or 4+) and anatomical criteria suitable for endovascular repair to percutaneous treatment with the MitraClip system (n = 184; Abbott Vascular, Santa Clara, CA) or surgical repair or replacement (n = 95). One- and two-year findings indicated that the primary efficacy endpoint of freedom from death, mitral valve surgery or reoperation, or 3+ or 4+ MR favored surgery. However, MitraClip therapy was safer and resulted in improvements in quality of life and New York Heart Association (NYHA) functional class that were as good as or better than surgery.

For the registry analysis, researchers led by Patrick L. Whitlow, MD, of the Cleveland Clinic (Cleveland, OH), enrolled symptomatic patients (MR 3+ or 4+) who were not candidates for surgery (predicted surgical mortality rate of 12% or more; n = 78). For comparison, the researchers retrospectively identified a group of MR patients (≥ 3+) with the same predicted surgical mortality rate who were screened but did not enroll in the registry or were not anatomically eligible for MitraClip device placement and received standard therapy (n = 36).

High-Risk Patients Show Benefit

At 30 days, mortality in the high-risk registry was 7.7% vs. the protocol-predicted rate of 18.2% (P = 0.006) and 14.2% per the Society of Thoracic Surgeons risk calculator (P = 0.06). Thirty-day mortality in the comparison group was 8.3%, which was not significantly different from the predicted rates (17.4% and 14.9%, respectively) or the MitraClip group. MitraClip device embolization did not occur during the study.

At 12 months, Kaplan-Meier survival was 75.4% in the MitraClip group vs. 55.3% in the comparison group (P = 0.047). In addition, MitraClip patients available for follow-up showed improvement over baseline in MR grade ≤ 2+, NYHA functional class, quality of life, LV parameters, and CHF hospitalizations (table 1).

Table 1. EVEREST II High Risk Registry 12-Month Outcomes for MitraClip Group

 

Baseline
(n = 78)

12 Months
(n = 56)

P Value

MR Grade ≤ 2+

1.3%

77.8%

< 0.0001

NYHA Class
I/II
III/IV

 
10.2%
89.8%

 
74.1%
25.9%

 
< 0.0001
< 0.0001

Quality of Life (SF-36 Score)
Physical Component
Mental Component

 

31.6 ± 9.1
44.2 ± 12.6

 

36.5 ± 10.6
49.2 ± 12.0

 

0.01
0.06

LV End Diastolic Volume, mL

166 ± 51

140 ± 43

< 0.001

LV End Systolic Volume, mL

80 ± 43

72 ± 36

0.001

CHF Hospitalizations (per patient year)

0.65

0.36

0.018


Diastolic and systolic septal-lateral annular dimensions also were reduced at 12 months (P < 0.0001 and P = 0.0008, respectively). There were no surgeries performed in the MitraClip group through 1 year.

“The data . . . suggest a role for the MitraClip device in treating symptomatic patients with 3 to 4+ MR who are at high risk of mortality with [mitral valve] surgery. MitraClip device placement in this selected high-risk group is feasible, effective in reducing symptoms and improving clinical status, and relatively safe in patients who otherwise have no safe option to reduce MR,” the researchers conclude.

Dr. Whitlow and colleagues also note that the improvements in LV diastolic and systolic volumes in addition to the reduced mitral annular dimensions indicate an early reversal of LV remodeling with MitraClip therapy, suggesting that “the degree of reduction in MR obtained . . . is hemodynamically important.” They note that long-term follow-up is needed to confirm the durability of the benefits observed at 12 months.

Lack of Adequate Control Group Problematic

In an accompanying editorial, Zoltan G. Turi, MD, and Michael Rosenbloom, MD, both of Cooper University Hospital (Camden, NJ), call the study “very important” but point out major caveats. They note the comparison group as a significant weakness, with over half failing to meet registry anatomic criteria. In addition, “patients were selected retrospectively and included only a subset of those eligible, the sample size was small, events were not adjudicated by the clinical events committee, and no information is provided on patient management or any other outcomes parameter except survival,” they point out.

Also, the editorial calls the study results “somewhat nuanced,” with a relatively high procedure-related mortality rate (8%) for a percutaneous approach, as well as high rates of MR ≥ 2+ through hospital discharge and at 1 year.

Still, the results are positive enough to warrant the MitraClip procedure’s continued use, “albeit only if performed under investigational protocols by operators skilled at transseptal puncture and working in institutions with extensive experience in percutaneous structural heart interventions as well as a proven track record with mitral valve repair in at least moderate-risk patients,” the editorial cautions.

Betting on the Wrong Horse?

Steven F. Bolling, MD, of the University of Michigan Medical School (Ann Arbor, MI), agreed with the editorial’s points. “They have no real control group, they have this sort of funky thing they’ve named a concurrent comparator group,” he told TCTMD in a telephone interview. “I’ve never heard of that. It was recruited retrospectively, and that’s like betting on a horse race after it’s happened.”

In addition, Dr. Bolling questioned the EVEREST II standard for success of MR 2+. “If I did surgery on you and left 2+ MR at the end, everyone would be upset,” he said. “But is it okay in these high-risk patients? It may be, but we don’t know that answer yet, that’s why I would call this study an interesting prelude.”

Nevertheless, the registry data should be viewed in a positive light. “I’m a surgeon, and I’m very much in favor of the MitraClip,” Dr. Bolling said. “I think there are high-risk patients with functional mitral disease related to changes in ventricular geometry where this is going to be a very good tool.”

FDA Prospects Debated

However, US Food and Drug Administration (FDA) approval will most likely not come from the current dataset, he noted. “If I’m the FDA commissioner, would I say, ‘Yes, I’ll approve this’? I don’t think so,” Dr. Bolling said. “This study begs us to do a randomized trial of the MitraClip in high-risk patients.”

Dr. Whitlow was more optimistic, expecting data to be presented to the agency within the next 8 to 10 months. “I think there’s enough data to at least get some kind of [investigational device exemption] approval,” he said in a telephone interview with TCTMD. “There are now 211 patients in all the EVEREST trials that are high risk according to the same definition. This is just the first 78. Data from the whole group look promising and that’s what will be presented to FDA.”

However, he acknowledged the study’s limitations. “Certainly for definitive data, you’d love to see a randomized trial, but these patients are never going to get randomized to surgery because they’re poor candidates. There’s [also] not a good medical control group that we can look at. The [comparison] group here is very small, and it’s hard to draw sweeping conclusions, but the data we’ve got are very encouraging. What we’ve proved is that this clip is a safe option and makes a significant number of these patients who don’t really have any alternatives much, much better.”

 


Sources:

1. Whitlow PL, Feldman T, Pedersen WR, et al. Acute and 12-month results with catheter-based mitral valve leaflet repair. The EVEREST II (Endovascular Valve Edge-to-Edge Repair) high risk study. J Am Coll Cardiol. 2012;59:130-139.

2. Turi ZG, Rosenbloom M. An option for the high-comorbidity patient with mitral regurgitation. J Am Coll Cardiol. 2012;59:140-142.

 

Disclosures:

  • The study is sponsored by Abbott Vascular.
  • Dr. Whitlow reports receiving research support from Abbott Vascular for enrolling patients in the EVEREST trials.
  • Dr. Turi reports receiving grant support from Abbott Vascular and St. Jude Medical for research unrelated to valvular heart disease and serving as a consultant for St. Jude Medical.
  • Dr. Rosenbloom reports serving as a consultant for Edwards Lifesciences and St. Jude Medical.
  • Dr. Bolling reports no relevant conflicts of interest.

 

Related Stories:

  1. Clip Device Effective for Both Functional, Degenerative Mitral Regurgitation
  2. Clip Device for Mitral Regurgitation Just as Effective as Surgery, with Improved Safety

 

 

Jason R. Kahn, the former News Editor of TCTMD, worked at CRF for 11 years until his death in 2014…

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