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July 3, 2023
COAPT 5-Year Data Demonstrate Benefits of Mitral TEER, Reveal Need to Address Underlying LV Dysfunction
July 3, 2023—In the COAPT trial, patients with heart failure (HF) and moderate-to-severe/severe secondary mitral regurgitation (MR) who remained symptomatic despite maximum medical therapy dose were randomized to undergo mitral transcatheter edge-to-edge repair (TEER) or receive guideline-directed medical therapy (GDMT) alone. In 5-year outcomes data published in The New England Journal of Medicine, Stone et al found that mitral TEER led to lower rates of HF hospitalization and all-cause mortality through 5-year follow-up compared to GDMT.1
KEY FINDINGS
- Based on these 5-year outcomes, mitral TEER with the MitraClip is safe and effective in patients with moderate-to-severe or severe secondary MR, with lower rates of hospitalization for HF and all-cause mortality compared to GDMT alone.
- There was improved prognosis for patients in the control group who crossed over to TEER treatment, as allowed per protocol at 2 years, but nearly half of control patients died before reaching the threshold for crossover eligibility.
- Death or hospitalization for HF occurred in 73.6% of TEER patients and 91.5% of control patients within 5 years, pointing to a need for further study to address underlying LV dysfunction
COAPT is a multicenter, parallel-controlled, open-label trial of 614 patients randomized between December 27, 2012, and June 23, 2017, from 78 United States and Canada centers. Patients were randomized to receive TEER with the MitraClip (Abbott) plus GDMT (n = 302) or the control group (n = 312) to GDMT alone. The sponsor funded the trial and participated in site selection and in data management and analysis.
Clinical and echocardiographic follow-up took place at 30 days, 6 months, 1 year, 18 months, and 2, 3, 4, and 5 years. Medication use was similar between groups during follow-up, although inhibitors of the renin–angiotensin axis were used more frequently in the device group. Major medication changes were infrequent in both groups, and the average daily dose of medication was similar for the device and control groups.
The primary effectiveness endpoint was all HF hospitalization through 2 years post-randomization. The primary safety endpoint was freedom from device-related complications at 12 months.
Follow-up through 5 years was completed in 89.4% of device patients and 84.6% of control patients. At least one HF hospitalization occurred in 151 (50%) device patients and 208 (66.7%) control patients, with a total number of 314 and 447 hospitalizations for HF within 5 years, respectively. The annualized HF hospitalization rate for the device versus control group was 33.1% and 57.2% (hazard ratio [HR], 0.53; 95% CI, 0.41-0.68), respectively.
All-cause mortality through 5 years occurred in 162 (57.3%) patients in the device group and 189 (67.2%) in the control group (HR, 0.72; 95% CI, 0.58-0.89). Death or hospitalization for HF through 5 years occurred in 213 (73.6%) and 266 (91.5%) patients (HR, 0.53; 95% CI, 0.44-0.64), respectively.
In terms of safety, 5-year freedom from device-related complications was 89.2%, with device-specific events in 4 (1.4%) patients, all of which occurred within 30 days postprocedure.
On echocardiography at 5 years, patients in the device group had less severe MR but slightly higher mean mitral valve gradient and smaller mitral valve orifice area. However, no patient required surgery or intervention for severe mitral stenosis.
After 2 years, the trial protocol allowed for crossover treatment with TEER in eligible patients; 67 (21.5%) control patients underwent mitral TEER. Investigators reported that after crossover treatment, MR and event rates were similar to patients in the device group. Device treatment in the original control group was an independent predictor of freedom from subsequent death or hospitalization (HR, 0.53; 95% CI, 0.36-0.78), and there were no device-specific safety events.
It was concluded that TEER of the mitral valve was safe, improved outcomes, and was associated with reductions in risks of death or HF hospitalization; however, adverse outcomes occurred in both groups, emphasizing a need for further therapies to address the underlying left ventricular (LV) dysfunction in this high-risk population.
1. Stone GW, Abraham WT, Lindenfeld J, et al; COAPT Investigators. Five-year follow-up after transcatheter repair of secondary mitral regurgitation. N Engl J Med. 2023 Jun 1;388(22):2037-2048. doi: 10.1056/NEJMoa2300213
CARDIAC INTERVENTIONS TODAY ASKS…
Study Principal Investigator Gregg Stone, MD, with Mount Sinai Heart Health System in New York, New York, provided some insight into the study results and their relevance for future practice and research.
What were the most impactful findings from the 5-year data, and how do these outcomes fit in among the current literature for HF patients with secondary MR?
First, mitral TEER with the MitraClip device provided a durable reduction in MR through 5 years. This was important to see because the primary anatomic derangement that causes functional or secondary MR in patients with HF is lack of coaptation of the mitral leaflets. Once this is restored by the MitraClip device, MR is reduced in nearly all patients, even long-term if the left ventricle continues to deteriorate as part of the natural history of cardiomyopathy. This resulted in a lasting reduction in death and HF hospitalizations and improved quality of life through 5 years with MitraClip treatment. However, event rates were high even with reduction in secondary MR due to the underlying left ventricular dysfunction that the MitraClip does not directly address. Thus, we need additional novel therapies for patients with HF—GDMT and MitraClip are important advances, but they’re not enough.
Although crossover patients had an improved prognosis, nearly half of the control group died before eligibility, reinforcing the need for prompt identification of patients appropriate for treatment. What did the study results reveal about patient selection criteria and determining which patients would benefit most from treatment with TEER?
All of the patient subgroups that were enrolled in the trial benefitted, including younger and older patients, men and women, those at low and high surgical risk, those with severely versus only mildly reduced left ventricular function, etc. What we can’t say for certain is which patients would have benefitted from treatment of secondary MR who were excluded from enrollment, such as those who were asymptomatic or had pure atrial MR, cardiogenic shock, severe right ventricular dysfunction, etc. Data from registries are suggesting that some of these patient groups do benefit, but we need more studies.
Would use of current GDMT strategies impact the approach to treating these patients?
When we ran COAPT, neprilysin inhibitors were used rarely and sodium-glucose cotransporter 2 inhibitors not at all. Had these drugs been available, some patients with HF and secondary MR would have improved sufficiently that they would not have needed TEER. However, for those who remained symptomatic with severe MR despite better GDMT, I am confident that the MitraClip would have had the same beneficial effect seen in COAPT.
You note that despite the risk-benefit profile of mitral TEER, the 5-year mortality/HF hospitalization rates for the device group point to a need to better address the underlying disease in these patients. What might research focused on this look like?
As I mentioned above, TEER is an important step because mitigating severe secondary MR in HF does substantially improve event-free survival and quality of life. However, we still need more potent therapies for the underlying left ventricular cardiomyopathy, which the MitraClip does not address. New therapies include inter-atrial shunts, cardiac contractility modulation, electrical or endovascular baroreflex activation, left ventricular reshaping, permanent ventricular assist devices, and more. The future is very exciting, and I am optimistic that we will continue to improve the prognosis for patients with HF, with or without severe secondary MR.
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