Heart failure (HF) patients with functional mitral regurgitation (MR) given transcatheter mitral valve repair (TMVr) with MitraClip continued to see benefits over those on guideline-directed medical therapy (GDMT) alone at 36 months in the COAPT study.
This is according to a new analysis with support and funding from the device’s manufacturer, Abbott, published online on Monday in the March 2 issue of the Journal of the American College of Cardiology.
The latest study also found that the 58 control subjects in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) who were allowed to cross over at 24 months derived similar benefit.
It follows 24-month results showing MitraClip resulted in fewer HF hospitalizations (HFHs) compared with GDMT alone, and lower mortality in HF patients with MR secondary to left ventricular (LV) dysfunction.
Secondary MR, also referred to as functional MR, in patients with HF and LV dysfunction is associated with increased mortality and HFHs and decreased quality of life, according to study authors led by Michael J. Mack, MD, from Baylor Scott & White Heart Hospital Plano, Texas.
The COAPT trial enrolled 614 HF patients from December 2012 through June 2017 with moderate-to-severe secondary MR who remained symptomatic despite maximally tolerated doses of GDMT. They were randomized to either TMVr with MitraClip (302 patients) or continued standalone GDMT (312 patients). The patients’ mean age was 72 ± 11.2 years, 36% were women, and 36.5% had previously undergone cardiac resynchronization therapy.
The MitraClip procedure – under general anesthesia – is performed using fluoroscopic and echocardiographic guidance via femoral access. A steerable guide catheter is advanced across the interatrial septum, and the MitraClip device is opened in the left atrium and advanced across the mitral valve into the ventricle before being pulled back to grasp the leaflets.
Beside lower HFH and mortality rates, the procedure was shown to be safe at 24 months and improved quality of life and functional capacity compared with GDMT; however, the researchers stressed that the sustainability of these benefits at longer-term follow-up was unknown.
At 36 months, data were available in 231 of 250 (92.4%) of eligible patients in the TMVr group and for 235 of 269 (87.4%) in the GDMT alone group. By this point, 42.8% of the device group had died from any cause, compared to 55.5% of the control group (hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.52 to 0.85; p = 0.001; number needed to treat [NNT] = 7.9; 95% CI: 4.6 to 26.1).
The 36-month analysis showed annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (R: 0.49; 95% CI: 0.37 to 0.63; p < 0.001).
The NNT with TMVr to prevent one hospitalization within 36 months was 3 (95% CI: 2.4 to 4.0), compared to 3.1 (95% CI: 1.9 to 8.2) in the GDMT alone group.
Patients who underwent TMVr also had sustained 3-year improvements in MR severity, with 98.8% of patients at 36 months in the treatment group (85/86) maintaining MR grade of ≤2+, as compared to 99.4% (161/162) at 24 months.
Quality-of-life and functional capacity measures were also sustained, the researchers noted.
By the 36-month mark, 58 patients who had been originally assigned to the GDMT control group were allowed to cross over and receive TMVr treatment. The composite rate of mortality or HFH was reduced in this group compared to GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).
“In patients with severe secondary MR and HF, transcatheter MitraClip repair reduced the severity of regurgitation and HFHs and improved functional capacity, quality of life, and survival over 3 years, compared with medical therapy without valvular intervention,” the researchers concluded.
The research into clinical outcomes should now continue beyond 36 months, they said, adding that further assessment of the impact of TMVr on patients with more or less severe MR, additional comorbidities and other types of valvular devices is needed.
The results of the COAPT trial were heavily scrutinized following dissimilar findings from the MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial, which did not find any benefit for MitraClip versus medical therapy alone in HF patients with severe functional MR, according to an accompanying editorial.
“The marked differences in trial results between COAPT and MITRA-FR have sparked 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,” said Rochester Regional Health’s Jeremiah P. Depta, MD, MPHS, and Harvard Medical School’s Deepak L. Bhatt, MD, MPH.
Still, they stressed that mitral valve leaflet approximation with either MitraClip or the PASCAL device from Edwards Lifesciences – a company for whom Depta has consulted – is the leading approach for TMVr.
The contrasting results from MITRA-FR mean it is crucial that patients selected for TMVr “model patients in the COAPT trial,” the editorialists said.
In any case, they added that: “The future of TMVr for patients with heart failure with functional MR remains promising, and this technology should be an important consideration in the management of these patients going forward.”
Mack MJ, Lindenfeld J, Abraham WT, et al. 3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure. J Am Coll Cardiol 2020;77:1029-40.
Depta JP, Bhatt DL. Crossover in COAPT: Does This Extend the Reach of TMVr for Treating Functional MR? J Am Coll Cardiol 2020;77:1041–3.