Late-breaking data presented at the American College of Cardiology's 59th annual scientific session from the landmark EVEREST II (Endovascular Valve Edge-to-Edge REpair STudy) trial demonstrated that Abbott's investigational MitraClip system met both its primary safety and effectiveness endpoints, suggesting that the minimally invasive MitraClip procedure may be an important treatment option for patients with significant mitral regurgitation (MR). At one 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.

The MitraClip system includes a catheter-based device, which is delivered to the heart through a blood vessel in the leg (femoral vein). The MitraClip device is designed to reduce significant MR by clipping together the leaflets of the mitral valve (one of the four valves of the heart). MR is the most common type of heart valve insufficiency and occurs when the leaflets of the mitral valve do not close completely, causing blood to flow backwards and leak into the left atrium of the heart during the cardiac cycle. To maintain an adequate forward flow of blood throughout the body, the heart compensates by increasing the size of the left ventricle (main pumping chamber of the heart) to accommodate the increase in the volume of blood it is pumping.

Mitral regurgitation affects more than 8 million people in the United States and Europe and is currently managed with drugs or open heart surgery, depending on an individual patient's severity of MR and risk factors. Significant MR is a debilitating condition where the heart's ability to function continues to deteriorate over time, and may lead to irregular heartbeat, heart failure, stroke, heart attack or death.

"In the EVEREST II trial, the catheter-based system exhibited a highly favourable safety profile, while providing meaningful and sustained clinical benefits," said Ted Feldman, M.D., FSCAI, director, Cardiac Catheterization Laboratory, and The Mr. and Mrs. Charles R. Walgreen Chair in Interventional Cardiology, NorthShore University HealthSystem, Evanston, IL; and co-principal investigator of the EVEREST II trial. "The positive trial results validate my experience that the procedure is a valuable therapeutic option for select patients with mitral regurgitation. 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 trials primary safety endpoint of major adverse events (MAEs) at 30 days, the MitraClip system demonstrated a superior safety profile (p<0.0001) compared to surgical repair or replacement (9.6 per cent of MitraClip patients and 57.0 per cent of surgery patients had an MAE). Major adverse events is defined as a composite of 12 pre-specified adverse events. In the primary effectiveness endpoint, the MitraClip device was non-inferior to surgery at one year (clinical success rate of 72.4 percent for MitraClip patients with successful initial treatment compared to a clinical success rate of 87.8 percent for surgery patients). With 95 percent confidence, the clinical success rate of the MitraClip device falls within 25.4 per cent of the clinical success rate of the surgical control. In the primary effectiveness endpoint, the clinical success rate is defined as freedom from death, surgery for valve dysfunction and moderate to severe MR (greater than 2+) at one year in patients with successful initial treatment.

At one 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 per cent of patients improving to mild (grade 1+) or moderate (grade 2+) MR whereas at baseline 95.6 percent of patients had moderate-to-severe (grade 3+) or severe (grade 4+) MR (p<0.0001)

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 per cent (p<0.0001) and left ventricular diastolic dimensions decreased a significant 6.4 per cent (p<0.0001) compared to baseline.

An improvement in symptoms, with 97.5 per cent of patients exhibiting no symptoms (NYHA Functional Class I) or mild symptoms (NYHA Functional Class II) [p<0.0001], whereas at baseline, 52.6 per cent 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 Survey (increase of 4.7 points in the physical quality of life score [p<0.0001] and increase of 5.8 points in the mental quality of life score [p<0.0001]).
"The EVEREST II safety and effectiveness results support the MitraClip device as a treatment choice, and show that MitraClip patients still have the option for successful mitral valve surgery afterward if needed," said Donald Glower, M.D., professor of surgery, Cardiovascular and Thoracic Surgery Division, Duke University School of Medicine, Durham, NC; and co-principal investigator of the EVEREST II trial. "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."

"When treating patients with significant MR, clinicians need to consider the benefits of the available treatment options and an individual patient's risk factors to determine the best course of therapy," said Charles A. Simonton, M.D., FACC, FSCAI, divisional vice president, Medical Affairs, and chief medical officer, Abbott Vascular. "Based on the positive risk-benefit profile demonstrated in the EVEREST II randomized trial and other EVEREST trials, the MitraClip procedure has the potential to be an important addition to the current options for treating 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 multi-center, randomized clinical trial of 279 patients with moderate-to-severe (3+) or severe (4+) mitral regurgitation who were candidates for mitral valve surgery. The mean age for patients was 68 years, and patients in the trial tended to have more co-morbidities, such as hypertension and congestive heart failure, than the average surgical patient as defined by the 2008 Society for Thoracic Surgeons (STS) 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 (ACC)/ American Heart Association (AHA) 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 (UCSF) reviewed the trial's echocardiograms based on the American Society of Echocardiography (ASE) criteria for assessment of MR and left ventricular function.

MR is the most common type of heart valve insufficiency in the United States and Europe, affecting millions of people worldwide. MR affects more than 8 million people in the U.S. and Europe. There are more than 600,000 new diagnoses of significant MR each year in the US and Europe; however, only about 20 per cent of these patients undergo surgery each year. While many patients are either higher-risk surgical patients or not sick enough for surgery, approximately 80 percent of patients with MR continue to be affected by the chronic volume overload caused by MR, which requires the heart to work harder, and may ultimately lead to heart failure and other complications.