What is the U.S. trial comparable to the European MITRA‑FR study?

The U.S. Comparable Trial to MITRA-FR is COAPT

The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial is the U.S. study that directly parallels the European MITRA-FR trial 1, 2.

Key Trial Characteristics

Both trials evaluated the same intervention—transcatheter edge-to-edge repair (TEER) with the MitraClip device—for secondary mitral regurgitation in heart failure patients, but they produced dramatically different results:

COAPT Trial (U.S./Canada)

• Conducted in the United States and Canada 2
• Randomized 614 patients with heart failure and secondary MR to MitraClip plus medical therapy versus medical therapy alone 1, 2
• Demonstrated significant benefit:
  • 47% reduction in heart failure hospitalizations at 2 years (35.8% vs 67.9%; HR: 0.53; P < 0.001) 1
  • 38% reduction in all-cause mortality at 2 years (29.1% vs 46.1%; HR: 0.62; P < 0.001) 1
  • Benefits sustained at 5-year follow-up 1

MITRA-FR Trial (France)

• Conducted in France 2
• Randomized 304 patients with similar disease to MitraClip plus medical therapy versus medical therapy alone 1
• Showed no benefit: No difference in all-cause mortality or HF hospitalization at 1 year (54.6% vs 51.3%; HR: 1.16; P = 0.53) 1

Why the Divergent Results Matter

The critical differences between these trials explain their opposing conclusions 1, 2:

Patient Selection (The "Proportionality Hypothesis"):

• COAPT patients had "disproportionate" MR: More severe regurgitation (EROA 0.41 cm²) relative to less LV dilation (LVEDV 101 mL/m²) 1
• MITRA-FR patients had "proportionate" MR: Less severe regurgitation (EROA 0.31 cm²) relative to more LV dilation (LVEDV 135 mL/m²) 1
• This suggests COAPT selected patients where the valve was the primary problem, while MITRA-FR selected patients where ventricular disease dominated

Medical Therapy Rigor:

• COAPT mandated maximally tolerated guideline-directed medical therapy verified by a heart failure specialist 2
• MITRA-FR had more variable HF medication use that was allowed to change during follow-up 2

Procedural Expertise:

• COAPT was conducted in comprehensive heart valve centers with prior MitraClip experience, resulting in lower rates of residual MR 2

Clinical Implications

The FDA approval for MitraClip in secondary MR (March 2019) integrated both trials 2, restricting use to symptomatic patients with:

• Moderate-to-severe or severe secondary MR (grade ≥3+)
• LVEF 20-50%
• LV end-systolic dimension <70 mm
• Persistent symptoms despite maximally tolerated GDMT as determined by an experienced multidisciplinary team 2

This approval essentially favors the COAPT patient phenotype—those with disproportionately severe MR relative to their ventricular size who have been optimized on medical therapy.