EVEREST II Data Presented at ACC for Abbott Vascular's MitraClip System

March 14, 2010—Abbott Vascular (Santa Clara, CA) announced data from the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) trial demonstrated that the company's investigational MitraClip system met both its primary safety and effectiveness endpoints, suggesting that the MitraClip procedure may be an important treatment option for patients with significant mitral regurgitation (MR). The MitraClip system includes a catheter-based transfemoral device designed to reduce significant MR by clipping together the leaflets of the mitral valve. Ted Feldman, MD, coprincipal investigator of the EVEREST II trial, presented the late-breaking data at the American College of Cardiology's 59th annual scientific session in Atlanta, Georgia.

At 1 year, the MitraClip device demonstrated meaningful clinical benefits for patients with significant MR, including improvements in heart function, quality of life, and normal physical activity and a decrease in cardiac symptoms. The EVEREST II trial is the first randomized trial of any minimally invasive mitral valve repair device compared to mitral valve surgery.

"In the EVEREST II trial, the catheter-based system exhibited a highly favorable safety profile while providing meaningful and sustained clinical benefits," commented Dr. Feldman. "The positive trial results validate my experience that the procedure is a valuable therapeutic option for select patients with MR. The therapy has the potential to transform the lives of thousands of patients and enable some to go from bed rest to a more active lifestyle."

In the EVEREST II trial's primary safety endpoint of major adverse events (defined as a composite of 12 prespecified adverse events) at 30 days, the MitraClip system demonstrated a superior safety profile (P < .0001) compared to surgical repair or replacement (9.6% of MitraClip patients and 57% of surgery patients had an major adverse event).

In the primary effectiveness endpoint, the MitraClip device was noninferior to surgery at 1 year (clinical success rate of 72.4% for MitraClip patients with successful initial treatment compared to a clinical success rate of 87.8% for surgery patients). The clinical success rate of the MitraClip device falls within 25.4% of the clinical success rate of the surgical control, with a 95% confidence interval. In the primary effectiveness endpoint, the clinical success rate is defined as freedom from death, surgery for valve dysfunction, and moderate-to-severe MR (> 2+) at 1 year in patients with successful initial treatment.

At 1 year, the MitraClip procedure demonstrated meaningful clinical benefits in the following secondary endpoints in patients with successful initial treatment:

• A reduction in the severity of MR, with 81.5% of patients improving to mild (grade 1+) or moderate (grade 2+) MR whereas at baseline 95.6% of patients had moderate-to-severe (grade 3+) or severe (grade 4+) MR (P < .0001).
• A reduction in both the volume (left ventricular diastolic volumes) and the diameter of the left ventricle heart chamber (left ventricular diastolic dimensions), indicating an improvement in heart function. Left ventricular diastolic volumes decreased a significant 13% (P < .0001), and left ventricular diastolic dimensions decreased a significant 6.4% (P < .0001) compared to baseline.
• An improvement in symptoms, with 97.5% of patients exhibiting no symptoms (New York Heart Association [NYHA] functional class I) or mild symptoms (NYHA functional class II) [P < .0001], whereas at baseline, 52.6% of patients had moderate symptoms (NYHA functional class III) or severe symptoms (NYHA functional class IV). Patients who are classified as NYHA functional class III or IV experience marked or severe limitations in physical activity.
• Meaningful improvements in both physical and mental quality of life compared to baseline as measured by the SF-36 health survey (increase of 4.7 points in the physical quality of life score [P < .0001] and increase of 5.8 points in the mental quality of life score [P < .0001]).

Coprincipal investigator Donald Glower, MD, stated, "The improvements in symptoms, quality of life, and cardiac function shown in the EVEREST II trial suggest the MitraClip procedure may be another valuable treatment option for certain patients with significant MR."

The MitraClip system received CE Mark in March 2008. The MitraClip device is an investigational device in the United States and is currently under review for approval by the US Food and Drug Administration (FDA).

The EVEREST II pivotal trial is a multicenter, randomized clinical trial of 279 patients with moderate-to-severe (3+) or severe (4+) MR who were candidates for mitral valve surgery. The mean age for patients was 68 years, and patients in the trial tended to have more comorbidities, such as hypertension and congestive heart failure, than the average surgical patient as defined by the 2008 Society for Thoracic Surgeons database.

Patients were selected for treatment with the MitraClip device if they met the criteria for surgical intervention from the 1998/2006 American College of Cardiology/American Heart Association Joint Task Force Recommendations regarding therapy for valvular heart disease. Patients had at least moderate-to-severe functional or degenerative mitral regurgitation and were either symptomatic or asymptomatic with evidence of compromised left ventricular function, atrial fibrillation, or pulmonary hypertension. The echocardiography core laboratory at the University of California, San Francisco, reviewed the trial's echocardiograms based on the American Society of Echocardiography criteria for assessment of MR and left ventricular function.

"As clinicians, we have seen our patients transformed from highly symptomatic to highly functional with a catheter procedure—and without a long hospital stay or a long recovery period," stated Dr. Feldman. "The real excitement is seeing our experience with individual patients reflected in trial results in a clear way."

On March 10, results from a study for the MitraClip were published by Olaf Franzen, MD, et al online ahead of print in the European Heart Journal. The investigators sought to assess acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients with an emphasis on adverse valve morphology and severe left ventricular dysfunction, as well as assess the feasibility of catheter-based mitral valve repair using the MitraClip system in high-surgical-risk patients with mitral regurgitation (MR) > grade 3+. The investigators concluded that mitral valve repair using the MitraClip system was shown to be feasible in patients at high surgical risk primarily determined by an adverse mitral valve morphology and/or severe left ventricular (LV) dysfunction.

As detailed in the European Heart Journal, MitraClip therapy was performed in 51 consecutive patients (age 73 ± 10 years; 34 [67%] men) with symptomatic functional (n = 35 [69%]) or organic MR (n = 16 [31%]). Mean logistic EuroSCORE was 29% ± 22%; Society of Thoracic Surgeons score was 15 ± 11. LV ejection fraction was 36% ± 17%. In 35 patients (69%), adverse mitral valve morphology and/or severe LV dysfunction were present. MitraClip implantation was successful in 49 patients (96%). Most patients (n = 34/49 [69%]) were treated with a single clip, whereas 14 patients (29%) received two clips and one patient received three clips. Mean device and fluoroscopy times were 105 ± 65 min and 44 ± 28 min, respectively. Procedure-related reduction in MR severity was one grade in 16 patients (31%), two grades in 24 patients (47%), and three grades in nine patients (18%). Forty-four of the 49 successfully treated patients (90%) showed clinical improvement at discharge (NYHA functional class > III in 48 patients [98%] before and 16 patients [33%] after the procedure [P < .0001]). There were no procedure-related major adverse events and no in-hospital mortality.