COAPT Substudy Spotlights QOL Gains With MitraClip

Patrice Wendling

March 22, 2019

NEW ORLEANS — To much acclaim, the COAPT trial demonstrated that use of the MitraClip (Abbott) in a very sick population with symptomatic (heart failure (HF) and secondary mitral regurgitation (MR) extends life and reduces HF hospitalization at 2 years. A new substudy suggests that quality of life, at least for those 24 months, was convincingly better than receiving standard care alone.

Among patients randomized to the MitraClip, the Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS) increased by an average of 15.9, 15.3, 14.5, and 12.8 points at 1, 6, 12, and 24 months, respectively (P < .001 for all). A gain of 5 points on the disease-specific questionnaire is considered a minimal clinically important difference (MCID).

All four KCCQ domains (physical limitation, total symptoms, quality of life, social limitations) improved significantly by 1 month, with the largest change occurring in the quality-of-life domain (mean change, 23.2 points).

Among patients randomly assigned to standard guideline-directed medical therapy alone, the KCCQ-OS also increased significantly, by an average 2.1, 5.3, 5.1, and 5.8 points at the same time points.

"The difference in health status between groups was moderately large, fully evident by 1 month, and generally sustained through 24 months," study author Suzanne V. Arnold, MD, PHA, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, said.

Similar results with the MitraClip were observed for the Short Form (SF)-36 physical and mental health summary scales, increasing 6.0 points and 4.2 points, respectively, at 1 month, with only slight attenuation over time. A 2.5-point increase is MCID on both scales.

No significant changes in either the SF-36 physical or mental scores were seen in the standard-care group (1-month change, 0.6 and 0.4, respectively), according to results reported here at the American College of Cardiology 68th Annual Scientific Session and simultaneously published online in the Journal of the American College of Cardiology.

The benefit of MitraClip was consistent across all subgroups, except for patients with ischemic cardiomyopathy, who derived significantly more benefit from the device than those with nonischemic cardiomyopathy (mean KCCQ-OS difference, 18.3 vs 8.4; for interaction = .02).

At 24 months, 39.3% of patients in the MitraClip group were alive, compared with 20.8% in the standard-care group. To account for this, the team performed categorical analyses that integrated health status and mortality and jointly modeled health status and mortality.

Categorical outcomes at 24 months showed that 36% of the MitraClip group was alive, with a moderately large improvement in KCCQ-OS of at least 10 points, compared with 17% for standard-care patients (number-needed-to-treat, 5.1; P < .001), Arnold said.

In the joint Bayesian analysis, the treatment benefit of transcatheter mitral valve repair (TMVR) with the MitraClip was greater than was estimated in the primary analysis at each time point — up on average 18.5, 18.6, 18.7, and 18.9 points at 1, 6, 12, and 24 months, respectively.

"Considering the previously reported benefits of TMVR on survival and heart failure hospitalization, these health status results further support the use of MitraClip for patients with heart failure and three- or four-[plus] secondary MR who remain symptomatic despite maximally tolerated guideline-directed medical therapy," Arnold concluded.

More Than Just Staying Alive

Panelist Mayra Guerrero, MD, Mayo Clinic, Rochester, Minnesota, remarked: "I think this finding is as important as, if not more important than, the primary end point, because…most patients don't just want to live longer unless they're going to feel better and they're going to have a decent quality of life."

From the physician's perspective, Guerrero said she is not concerned that American physicians will be able to implant the device for secondary MR because of the experience in primary MR, which is more technically demanding. In light of the recent expanded indication for the MitraClip in secondary MR, however, the question is: "Who should be at the table making these decisions and how can we predict who is going to feel better and have a better quality of life?"

Arnold replied that it is a very difficult question and although data from COAPT and MITRA-FR are available to determine a mortality and heart failure benefit, there isn't the corollary in health status.

"Just looking at subgroups, we don't really see much heterogeneity," she said. "Obviously, some multivariable analyses [are needed] to try to understand who are the patients who are really going to benefit in terms of health status because it may be different than who is going to have a mortality benefit. And perhaps getting people feeling better for however long they have left makes the procedure worthwhile."

As MitraClip use in secondary MR becomes more widespread, registry data might also provide insights, Arnold said.

Panelist Blase Carabello, MD, chief of cardiology, East Carolina Heart Institute, Greenville, North Carolina, followed along the same lines, asking if there were patients Arnold was sorry that got clipped or wouldn't offer the procedure to in the future if she saw them again.

Arnold replied that she doesn't implant the MitraClip but noted that there are generally few postprocedural complications. "Again, I think looking at that heterogeneity in treatment effect, are there really people who don't benefit? I think it's still an unanswered question," she said.

Also unanswered is whether the presence or absence of atrial fibrillation (AF) — which the panel pointed out was present in about half of patients — affected health status or whether the MitraClip actually improved AF burden to any extent. In contrast to a previous study, Arnold said, "we did not see an effect of atrial fibrillation on health status outcomes in this study," but she did not have data on AF burden post-MitraClip.

Speaking with | Medscape Cardiology, Athena Poppas, MD, Rhode Island Hospital, Providence, said that "the more we can understand this trial and this population, the better we will be in designing future trials and caring for the patients. So I think these are useful data."

"How patients feel is as important as what we see on their echocardiogram," she said.

Nevertheless, it would be useful to have some objective data, such as the 6-minute walk test or frailty assessment, particularly as the placebo-effect has been shown in several trials to be quite powerful, she said.

As for why patients with ischemic cardiomyopathy appeared to derive greater benefit from the device, "mechanistically, you'd have to stretch a bit to find a reason for it," Poppas said.

COAPT was funded by Abbott. The health-status analysis was conducted independently at Saint Luke's Mid America Heart Institute. Arnold reports a career development grant from the National Institutes of Health/National Heart, Lung, and Blood Institute.

J Am Coll Cardiol. Published online March 17, 2019. Abstract

American College of Cardiology (ACC) 2019 Scientific Session. Presented March 17, 2019.

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