Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation (COAPT)

Authors, Journal, Affiliations, Type, DOI

• Authors: Gregg W. Stone, William T. Abraham, JoAnn Lindenfeld, Saibal Kar, Paul A. Grayburn, D. Scott Lim, Jacob M. Mishell, Brian Whisenant, Michael Rinaldi, Samir R. Kapadia, Vivek Rajagopal, Ian J. Sarembock, Andreas Brieke, Steven O. Marx, David J. Cohen, Federico M. Asch, Michael J. Mack, for the COAPT Investigators
• Journal: New England Journal of Medicine, Volume 388, Issue 22, Pages 2037–2048
• Affiliations: Icahn School of Medicine at Mount Sinai (Stone), Ohio State University (Abraham), Vanderbilt (Lindenfeld), and 78 sites in US and Canada
• Type: Multicenter randomized controlled trial — 5-year follow-up of the COAPT trial
• DOI: 10.1056/NEJMoa2300213
• Funded by: Abbott (MitraClip manufacturer)
• Published: March 5, 2023 (online); June 1, 2023 (print); ClinicalTrials.gov NCT01626079

Overview

The COAPT trial originally demonstrated 2-year benefits of transcatheter edge-to-edge repair (TEER) with MitraClip in patients with symptomatic heart failure and secondary mitral regurgitation (SMR) despite maximal GDMT. This 5-year follow-up confirms durable reductions in HF hospitalization (annualized 33.1% vs 57.2%/yr; HR 0.53) and all-cause mortality (57.3% vs 67.2%; HR 0.72), sustained across all major subgroups. However, treatment benefit was concentrated in the first 2–3 years; curve convergence thereafter was largely attributable to 44.9% of eligible control-arm patients crossing over to TEER after 2 years as permitted by protocol. Device safety was excellent (1.4% device-specific events, all within 30 days). The persistent high absolute event rate in both arms (73.6% of device group dead or hospitalized by 5 years) underlines that MitraClip reduces MR-driven volume/pressure overload but does not address the underlying LV cardiomyopathy.

Keywords

Transcatheter edge-to-edge repair, secondary mitral regurgitation, heart failure, MitraClip, COAPT, hospitalization, mortality, randomized controlled trial, guideline-directed medical therapy

Key Takeaways

Background and Pathophysiology

• Ischemic and nonischemic LV cardiomyopathy causes papillary muscle dislocation → mitral leaflet coaptation failure → SMR
• Severe SMR in LV dysfunction portends poor prognosis: increased HF hospitalization and reduced survival
• TEER reapproximates mitral leaflets and reduces MR without the leaflet structural abnormalities of primary MR
• The original 2-year COAPT results showed TEER was safe and improved outcomes vs maximal GDMT alone

Study Design

• Multicenter, randomized, parallel-controlled, open-label trial; 78 centers US and Canada
• Enrollment: December 2012 – June 2017; n=614 (302 device, 312 control)
• Device group: MitraClip TEER + guideline-directed medical therapy (GDMT)
• Control group: GDMT alone
• Randomization 1:1, stratified by cardiomyopathy etiology and site

Eligibility Criteria (COAPT)

• Ischemic or nonischemic cardiomyopathy
• LVEF 20–50%
• Moderate-to-severe (3+) or severe (4+) SMR confirmed by echocardiographic core laboratory
• Symptomatic (NYHA class II, III, or IVa ambulatory) despite stable maximal GDMT
• Prior revascularization, CRT, or ICD if indicated per guidelines
• Exclusion: LVESD >70 mm; severe pulmonary hypertension; moderate or severe symptomatic RV failure
• Centralized eligibility committee confirmed all criteria before randomization

Procedure and Technical Results

• TEER attempted in 293/302 patients (97.0%); ≥1 clip implanted in 287/302 (95.0%)
• Mean number of clips: 1.7 ± 0.7 (range 1–4)
• MR at discharge (in 260 patients with echo): MR ≤1+ in 82.3%; 2+ in 12.7%; 3+ in 3.5%; 4+ in 1.5%

Primary Effectiveness Results (5-Year)

• Total HF hospitalizations within 5 years: 314 device vs 447 control
• Days alive and out of hospital: 1123.5 ± 664.8 vs 894.8 ± 655.1 (device vs control)

Landmark Analyses

• HF hospitalization curves diverged until year 3, thereafter event rates similar between groups
• Mortality curves diverged until year 2, thereafter event rates similar
• Convergence attributable to crossover: 44.9% of eligible control patients underwent TEER after 2 years
• Nearly half the control group died before 2 years (before crossover eligibility)

Subgroup Consistency

• Benefit consistent across: age, sex, MR severity, LVEF, LV volume, cause of cardiomyopathy (ischemic vs nonischemic), surgical risk
• NYHA class I or II more frequent in device group throughout 5-year follow-up

Safety Results

• Freedom from device-related complications at 5 years: 89.2%
• Device-specific safety events: 4/293 patients (1.4%) — all within 30 days of procedure
• Severe mitral stenosis (VA <1.5 cm², core lab): 7.6% device vs 0% control — no surgery required
• Atrial septal defect requiring intervention: 0.7% device vs 0% control
• Unplanned mitral valve procedures: 11 device vs 75 control

Echocardiographic Results

• MR remained less severe in device group vs control throughout 5-year follow-up
• Mitral valve gradient higher and MVO area smaller in device group (expected post-TEER)
• Previous analyses showed valve gradient after TEER did not impair prognostic benefit
• LV chamber size, function, forward stroke volume, and RVSP similar between groups during follow-up

Crossover Analysis

• 67/312 control patients (21.5%) underwent TEER: 5 before 2 years, 62 after 2 years
• 62 crossovers = 44.9% of the 138 control patients eligible for crossover at 2 years
• 46.8% of surviving control patients at 2 years had MR ≤2+ (no longer severe → ineligible)
• Crossover predicted freedom from subsequent death/HF hosp (HR 0.53; 95% CI 0.36–0.78)
• Post-crossover event rates in control group approximated original device-group event rates

Medical Therapy Evolution

• Renin-angiotensin axis inhibitors used more in device group (improved hemodynamics post-TEER)
• ARNI (sacubitril-valsartan) use progressively increased during follow-up
• Only 3 patients treated with SGLT2i during trial (all in last year) — SGLT2i era gap

Limitations

• Open-label: Unblinded device treatment; withdrawal more frequent in control group (missing data handled by multiple imputation — results consistent)
• Industry funded: Abbott sponsored the trial; sponsor participated in data management/analysis
• SGLT2i underuse: Only 3 patients received SGLT2i — unclear impact on modern GDMT-optimized cohort
• First-generation MitraClip: Third-generation devices achieve higher rates of MR ≤1+; newer PASCAL device also approved for degenerative MR
• Crossover design: Protocol-permitted crossover after 2 years dilutes long-term between-group differences; the true "untreated" 5-year mortality is partially unknowable
• Narrow eligibility: LVEF 20–50%, LVESD ≤70 mm, PASP ≤70 mmHg, no severe RV failure — generalizability to more advanced HF or moderate MR uncertain
• Not designed to assess: Benefit in asymptomatic SMR or moderate (2+) SMR

Key Concepts Mentioned

• concepts/Secondary-Mitral-Regurgitation — primary subject; 5-year TEER outcomes
• concepts/Cardiac-Resynchronization-Therapy — mandatory prior to TEER if eligible; CRT done before enrollment

Key Entities Mentioned

• entities/Heart-Failure — primary population; high ongoing event rate even post-TEER

Wiki Pages Updated

• wiki/sources/mvteer-coapt-nejm-2023.md — created
• wiki/sourceindex.md — updated
• wiki/wikiindex.md — updated
• wiki/concepts/Secondary-Mitral-Regurgitation.md — updated with COAPT 5-year data