NEW ORLEANS — Transcatheter repair of functional mitral regurgitation (or secondary MR) with MitraClip improved quality of life and hemodynamics better than optimal medical therapy alone, COAPT trial analyses showed. Indeed, the COAPT QOL study showed that among patients with symptomatic HF and 3+ to 4+ secondary MR receiving maximally-tolerated medical therapy, edge-to-edge TMVr resulted in substantial early and sustained health status improvement compared with medical therapy alone.
Earlier, the spectacular results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial, that were presented at TCT 2018 had indicated that transcatheter mitral valve approximation using the MitraClip, on a background of maximally tolerated guideline-directed medical therapy (GDMT) was superior to GDMT alone in the reduction of Heart Failure (HF) hospitalization and mortality in symptomatic HF patients with grade 3-4+ Mitral regurgitation (MR). These landmark findings were published in the New England Journal of Medicine.
The COAPT trial was a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with NYHA class II-IVa HF despite treatment with maximally tolerated GDMT who had been determined by the site’s local heart team as not appropriate for MV surgery. The patient population was similar to the MITRA-FR study, presented at the ESC conference, where the results were negative. A total of 614 eligible subjects with HF and grade 3-4+ MR who remained symptomatic despite maximally tolerated GDMT at up to 100 investigational sites were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT in one arm and GDMT alone in the other. The COAPT trial completed patient recruitment in June 2017. The primary effectiveness endpoint was recurrent HF hospitalizations through 24 months, analyzed when the last subject completed 12-months of follow-up, powered to demonstrate the superiority of MitraClip therapy. The primary safety endpoint was a composite of device-related complications at 12 months, compared to a performance goal. The findings had shown that the primary effectiveness endpoint, which was the annual rate of all hospitalizations for heart failure within 24 months, for MitraClip + GDMT vs. GDMT, was 35.8% vs. 67.9% (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.40-0.70, p < 0.001). The primary safety endpoint, which was the rate of freedom from device-related complications at 12 months was 96.6% for MitraClip ( P<0.001). Moreover, the rate of all-cause mortality within 24 months occurred in 29.1% and 46.1% in the device and control groups respectively (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001). The investigators had concluded that transcatheter mitral valve approximation using the MitraClip on a background of maximally tolerated GDMT was superior to GDMT alone in reducing HF hospitalization and mortality in symptomatic HF patients with grade 3-4+ MR, with excellent safety.
“The durability of the effect is surprising. These patients don’t just have a valve that’s a problem. This is different from a regenerative MR population where the valve is the only issue. You fix the valve, and patients get remarkably better very quickly and you would expect that to stay. These patients still have underlying cardiomyopathy, they still have heart failure. And so, to see the effect being very durable over time is surprising and certainly supports its use.”- Dr. Suzanne V. Arnold, M.D.
However, beyond prolonging survival and reducing hospitalizations, improving patients’ health status (i.e., symptoms, functional status, quality of life) was a key treatment goal of TMVr. In fact, among older patients with comorbidities and high symptom burden, health status improvement was considered to be of greater importance to patients than improved survival. Hence, Suzanne V. Arnold and her colleagues aimed to understand the health status outcomes of patients with HF and 3+ to 4+ secondary MR treated with TMVr versus standard care. Health status was assessed at baseline and at 1, 6, 12, and 24 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey. The primary health status endpoint was the KCCQ overall summary score (KCCQ-OS; range 0 to 100; higher ¼ better; minimum clinically important difference ¼ 5 points).
The investigators found that at baseline, patients had substantially impaired health status (mean KCCQ-OS 52.4 ± 23.0). Health status remained substantially impaired on maximally-tolerated medication, with just a 2.1-point gain over the baseline 52.4 on the 100-point Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scale. But scores improved by a clinically-meaningful 16.9 points at 1 month after the transcatheter procedure. The advantage with MitraClip fell only slightly to 14.5 points at 12 months and 12.8 points at 24 months (all P<0.001 between groups), reported Suzanne Arnold, MD, of Saint Luke’s Mid America Heart Institute in Kansas City, Missouri, at the ACC meeting. The findings were simultaneously published online in the Journal of the American College of Cardiology. At 24 months, 36.4% of TMVr patients were alive with a moderately large (≥10-point) improvement versus 16.6% of standard care patients (p < 0.001), for a number needed to treat of 5.1 patients (95% CI: 3.6 to 8.7 patients). Quality of life gained the most from MitraClip, but all the other KCCQ domains improved significantly as well. Bayesian analysis to account for bias from differential mortality between groups likewise came out with a significant 18.9 point advantage to clipping. Moreover, generic health status measured on the Short Form 36 (SF-36) also favored intervention across time points. TMVr patients also reported better generic health status at each time point (24-month mean difference in SF-36 summary scores: physical 3.6 points; 95% CI: 1.4 to 5.8 points; mental 3.6 points; 95% CI: 0.8 to 6.4 points). Last but not the least, the proportion of patients alive with a “moderately large,” ≥10-point KCCQ score improvement, was 36.4% with MitraClip versus 16.6% with medication alone (P<0.001) at 24 months, for a number needed to treat of 5.1. Thus, Arnold et al. concluded that among patients with symptomatic HF and 3+ to 4+ secondary MR receiving maximally-tolerated medical therapy, edge-to-edge TMVr resulted in substantial early and sustained health status improvement compared with medical therapy alone. Previously reported primary results from the COAPT trial showed a significant reduction in both heart failure hospitalization and all-cause mortality at 24 months for MitraClip, which led to FDA approval for secondary mitral regurgitation on Thursday. However, doctors reiterated the cautious note sounded when the initial findings came out: patient selection and optimization of medical and implantable device therapy by a heart failure specialist as done in the trial will be key to achieving these results. They, however, did believe that further research was needed to understand the generalizability of these outcomes outside the setting of a clinical trial when deployed in less experienced centers.
“The big question is can you afford this? In my mind, I think we need to open our wallets for improving quality of life. If we can’t do that, we’re not doing good medicine and I know there is no question about us being cost conscious, but these are really sick patients. I want to congratulate the investigators for going that extra mile to look for quality of life, as it is very important. If we save a life, but the patient is in bed and not improving their quality, we didn’t really do a service to them.”- Dr. Roxana Mehran, M.D.
Speaking about what she found most surprising, in an interview with Dr. Roxana Mehran, Director of Interventional Cardiovascular Research and Clinical Trials at Mount Sinai School of Medicine, Dr. Suzanne Arnold remarked, “The durability of the effect is surprising. These patients don’t just have a valve that’s a problem. This is different from a regenerative MR population where the valve is the only issue. You fix the valve, and patients get remarkably better very quickly and you would expect that to stay. These patients still have underlying cardiomyopathy, they still have heart failure. And so, to see the effect being very durable over time is surprising and certainly supports its use.” Referring to the much-awaited cost-effectiveness results, Dr. Mehran stressed on the importance of cost, stating, “The big question is can you afford this? In my mind, I think we need to open our wallets for improving quality of life. If we can’t do that, we’re not doing good medicine and I know there is no question about us being cost conscious, but these are really sick patients. I want to congratulate the investigators for going that extra mile to look for quality of life, as it is very important. If we save a life, but the patient is in bed and not improving their quality, we didn’t really do a service to them.”
In a subsequent presentation at the same late-breaking clinical trial session, it was stated that left ventricular end systolic and end diastolic volumes and MR severity improvements were significantly better at 24 months with clipping than among controls. In an interview, Federico Asch, MD, of MedStar Health Research Institute in Washington, reported that all subgroups showed benefit across degree of left ventricular dysfunction and dimensions, pulmonary hypertension, and severity of tricuspid valve dysfunction. The only predictor of poor outcomes after MitraClip was right ventricular systolic pressure. He also provided the reassurance that while patients were not blinded to treatment assignment in COAPT, the effects were unlikely to represent placebo effects, given the magnitude of sustained health status benefit and the concordance of the results with other less subjective outcomes (including death and rehospitalization).
To watch the interview with Dr. Roxana Mehran, click here.
To watch the interview with Dr. Federico Asch, click here.
To view the slides, click here.
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