Continual positive outcomes back device use in COAPT follow-up

Transcatheter mitral leaflet approximation with the MitraClip device offered long-term benefits in heart failure (HF) patients with moderate-to-severe mitral regurgitation (MR) secondary to left ventricular dysfunction, according to follow-up COAPT trial results.

The annualized rates of HF hospitalizations per patient-year were 35.5% with transcatheter mitral valve repair (TMVr) and 68.8% with guideline-directed medical therapy (GDMT) alone for a hazard ratio of 0.49 (95% CI 0.37 to 0.63, P<0.001) and a number needed to treat (NNT) of 3.0 (95% CI 2.4 to 4.0), reported Michael J. Mack, MD, of Baylor Scott & White Heart Hospital Plano in Texas, and co-authors.

Mortality occurred in 42.8% of the device group versus 55.5% of the GDMT group (HR 0.67, 95% CI 0.52 to 0.85, P=0.001, NNT=7.9, 95% CI 4.6 to 26.1), they stated in the Journal of the American College of Cardiology.

Patients who underwent TMVr also saw three-year improvements in MR severity, quality-of-life (QOL) measures, and functional capacity, and those patients who crossed over to the device arm also saw a reduction HF hospitalization, they added.

Results from the 2018 COAPT trial led to the FDA approval of the MitraClip TMVr system for treatment of functional MR. “The present analysis extends [COAPT findings], demonstrating that through 36 months, TMVr continued to be safe and provided a durable reduction in MR, which resulted in fewer HF [hospitalizations] and deaths, with improved QOL and greater preservation of functional capacity compared with GDMT alone,” Mack’s group wrote.

Since the FDA green light, the TMVr market has taken off, with a value of a little over $250 million in 2019, a forecast value of $1.4 billion by 2028, and “neither the United States nor global [TMVr] market will be hugely impacted by the coronavirus (Covid-19) pandemic,” according to a report in Medical Product Outsourcing.

According to results from the EXPAND registry-based trial, outcomes with the next-generation MitraClip NTR and XTR systems compared favorably with those seen in the original COAPT study. In January 2021, the Centers for Medicare and Medicaid Services (CMS) extended reimbursement to include secondary (functional) MR resulting from HF. CMS renamed the TMVr National Coverage Decision to cover “mitral valve Transcatheter Edge-to-Edge Repair” for people with secondary MR who remain symptomatic despite GDMT.

In an editorial comment accompanying the current study, Jeremiah P. Depta, MD, MPHS, of the Sands Constellation Heart Institute, Rochester Regional Health in New York, and Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center in Boston pointed out that “A unique design of the COAPT trial was the prespecified analysis of patients randomized to GDMT alone who were allowed to crossover and undergo TMVr using the MitraClip at 24 months… MR was significantly reduced in patients who crossed over to the MitraClip.”

Depta and Bhatt praised Mack’s group for addressing the “inherent survivor bias” in these crossover patients by landmarking them “at the time of TMVr treatment (median follow-up: 7.7 months)… a time-dependent multivariable analysis revealed that crossing over to MitraClip was independently associated with freedom from death or heart failure hospitalization.”

They also noted that COAPT results differ enough from Mitra-FR trial data to bring on “significant debate and speculation regarding trial size, patient selection, anatomical and/or echocardiographic differences, operator experience, medical optimization, and hypotheses to account for the apparently contradictory trial results.” Findings from the ongoing RESHAPE-HF-2 (estimated study completion date March 2021) and MATTERHORN trials “should provide additional insights on TMVr for treating functional MR.”

COAPT randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to two arms: TMVr plus GDMT versus GDMT alone. The study’s primary effectiveness endpoint was all HF hospitalizations through 24-month follow-up; Mack and co-authors reported on patients followed for 36 months.

They reported that among 58 patients assigned to GDMT alone who crossed over to TMVr, the subsequent composite rate of mortality or HF hospitalization was reduced versus those who continued on GDMT alone (adjusted HR 0.43, 95% CI 0.24 to 0.78, P=0.006).

The authors also found that benefits with regards to improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and functional capacity assessments by 6-min walk distance (6MWD) previously reported at 12 months persisted through complete 24-month follow-up. Specifically, the change in KCCQ score from baseline to 24 months was 7.8 points in the device group versus -12.1 in the GMDT group (HR 20.0, 95% CI 13.7 to 26.2, P<0.0001), and -55 versus -93.5 (HR 38.5, 95% CI 8.3-68.7, P=0.01), respectively, for change in 6MWD.

Also, TMVr substantially cut the severity of MR compared with GDMT, with lasting effects for MR grade of ≤2+, and led to lower rates of multiple adverse events versus GDMT including:

  • 24 months: 99.9% in the device group versus 46% in the GDMT group (P<0.0001).
  • 36 months: 98.8% versus 79.6% (P=0.0002).
  • All-cause death: 42.8% versus 55.5% (HR 0.67, 95% CI 0.52 to 0.85, P=0.001).
  • HF death: 21.6% versus 34.7% (HR 0.51, 95% CI: 0.35 to 0.74, (P=0.0004).
  • All-cause hospitalizations: 77.7% versus 93.3% (HR 0.70, 95% CI 0.58 to 0.84, P=0.0001).

Mack’s group highlighted that “The absolute reduction of adverse events with TMVr in the COAPT trial (as reflected in the low NNT) was especially notable because all patients were treated with a maximally tolerated GDMT regimen. “

In terms of study limitations, the authors were in line the editorialists, noting that “many patients assigned to GDMT alone died before reaching the 2-year eligibility time point for MitraClip treatment, introducing the potential for survivorship bias in the outcomes of crossover patients,” but stressed that “the relative magnitude of benefit after late crossover in the GDMT alone group appeared to be similar to earlier treatment with the MitraClip in the unselected COAPT-eligible population in the device arm.”

They added that results from 5 years of follow-up in COAPT will shed light on “the durability of TMVr treatment in this patient population.” In the meantime, the authors advised that “COAPT-eligible patients with HF who remain symptomatic after medical therapy optimization should be considered for early MitraClip treatment to improve event-free survival.”

  1. In patients with severe secondary mitral regurgitation (MR) and heart failure (HF), transcatheter MitraClip repair reduced the severity of MR and HF hospitalizations, according to three years of follow-up in the COAPT trial.

  2. COAPT patients also experienced improved functional capacity, quality of life, and survival over three years, compared with medical therapy without valvular intervention.

Shalmali Pal, Contributing Writer, BreakingMED™

The study was supported by Abbott.

Mack reported relationships with, and/or support from, Abbott, AstraZeneca, CVRx, Edwards Lifesciences, Impulse Dynamics, Boehringer Ingelheim, VoluMetrix, and V-Wave. Co-authors reported relationships with, and/or support from, Abbott, Boehringer Ingelheim, Respicardia, Sensible Medical, CVRx, Impulse Dynamics, VWave Medical, Boston Scientific, Edwards Lifesciences, 4TECH, Medtronic, Boston Scientific, W.L. Gore, Neochord, CardioValve, 4C Medical, the Cardiovascular Research Foundation, Cook, Terumo, QOOL Therapeutics, Orchestra Biomed, Valfix, TherOx, VascularDynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech, Cagent, Applied Therapeutics, Biostar, SpectraWave, Cardiac Success, and MedFocus.

Depta reported relationships with Edwards Lifesciences, Boston Scientific, and WL Gore & Associates, as well as serving as J Am Coll Cardiol guest associate editor for the current paper. Bhatt reported relationships with, and/or support from, Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences, Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft, American Heart Association Quality Oversight Committee, the Baim Institute for Clinical Research/St. Jude Medical/Abbott, the Cleveland Clinic/Edwards, Duke Clinical Research Institute/Ferring Pharmaceuticals, Mayo Clinic, Mount Sinai School of Medicine/Daiichi-Sankyo, the Population Health Research Institute/Bayer, the American College of Cardiology (ACC), RE-DUAL PCI clinical trial/Boehringer Ingelheim, AEGIS-II executive committee/CSL Behring, Belvoir Publications/Harvard Heart Letter, HMP Global/Journal of Invasive Cardiology, J Am Coll Cardiol, Medtelligence/ReachMD, Level Ex, MJH Life Sciences, Slack Publications/ Cardiology Today’s Intervention, the Society of Cardiovascular Patient Care, WebMD, Clinical Cardiology, NCDRACTION Registry Steering Committee , VA CART Research and Publications Committee, Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLxPharma, Regeneron, Roche, Sanofi, Synaptic, The Medicines Company, Elsevier/Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease, Biotronik, Boston Scientific, CSI, St. Jude Medical/Abbott, Svelte, ACC, FlowCo, Merck, Novo Nordisk, and Takeda.

Cat ID: 914

Topic ID: 74,914,730,914,192,925