Updated–The final results of the highly anticipated EVEREST (Endovascular Valve Edge-to-Repair Study) II were presented by Ted Feldman at the ACC Scientific Sessions in New Orleans and published simultaneously in the New England Journal of Medicine. 279 patients with moderately severe or severe mitral regurgitation (MR) were randomized on a 2:1 basis to either percutaneous repair with the experimental MitraClip device or surgical repair or replacement of the valve.
At one year, compared to patients in the MitraClip group, patients in the surgery group were significantly more likely to be free of death, surgery for mitral-valve dysfunction, or grade 3+ or 4+ MR at 12 months– the primary efficacy endpoint of the trial– 55% in the MitraClip group versus 73% in the surgery group (p=0.007), Here are the rates for the individual components of the primary endpoint:
- Death: 6% in each group
- Surgery for mitral-valve dysfunction: 20% versus 2%
- Grade 3+ or 4+ MR: 21% versus 20%
Both groups had improvement in the severity of MR following treatment, but the improvement was significantly greater in the surgery group. At 30 days, the rate of major adverse events was 15% in the MitraClip group versus 48% in the surgery group (p<0.001). 23% of patients in the MitraClip group had significant MR prior to hospital discharge and were referred for surgery.
The authors summarized their results: “We found that although percutaneous treatment was effective at reducing mitral regurgitation, surgical treatment was more effective, as graded by an echocardiographic core laboratory. However, percutaneous treatment was associated with a reduction in the rate of major adverse events at 30 days, as compared with surgery, and with sustained clinical improvement, as measured by quality of life, heart failure status, and left ventricular function.”
In an accompanying editorial, Catherine Otto and Edward Verrier write that “ideally, any new procedure would also be at least equivalent to surgical valve repair in terms of safety, valve function, durability, and long-term outcomes.” The MitraClip, they write, “fullfills some, but not all, of these criteria.” They note that the introduction of new minimally invasive devices poses a challenge to the traditional model in which the cardiologist usually decides whether a patient should be referred for surgery. “This approach breaks down as more options for intervention become available,” they write. They propose, in response, a “patient-centered approach to decision making” that would require “a true consensus of experts” following a review of each case.
Update: At his ACC presentation Feldman also presented a second analysis that viewed the data as a comparison of treatment strategies in which mitral valve surgery following unsuccessful percutaneous repair was not considered an endpoint event. In this analysis, at 2 years the primary endpoint occurred in 62.7% of the MitraClip group versus 66.3% of the surgery group.
Here is the press release from Abbott:
Data from Landmark Clinical Trial of Abbott’s MitraClip® System Demonstrate Durable Clinical Benefits for Patients with Mitral Regurgitation Two Years After Treatment
· Positive EVEREST II Results Published in The New England Journal of Medicine and Presented at the American College of Cardiology Conference
· First-of-its-Kind, Catheter-Based Investigational Device for Mitral Valve Repair Improves Heart Function and Symptoms of Mitral Regurgitation
NEW ORLEANS – April 4, 2011 — Abbott today announced data from its EVEREST II (Endovascular Valve Edge-to-Edge REpair STudy) study showing that patients with significant mitral regurgitation (MR) treated with the company’s investigational percutaneous catheter-based MitraClip® system continue to demonstrate the clinical benefits of initial treatment shown at one year out to two years, including improvements in heart function and reductions in symptoms. EVEREST II is the first randomized clinical trial to compare a catheter-based mitral valve device to mitral valve surgery. Data from the study were published in The New England Journal of Medicine and presented in a late-breaking clinical trial session at the American College of Cardiology’s (ACC) 60th Annual Scientific Session and i2 Summit 2011 in New Orleans.
At two years after treatment, data from 279 patients from the EVEREST II trial demonstrated a clinical success rate of 51.7 percent for patients treated with the MitraClip device compared to a clinical success rate of 66.3 percent for surgery patients (p=0.04) on an Intention-to-Treat (ITT) basis. These results compare with the one-year data, which demonstrated a clinical success rate of 55.2 percent for patients who received the MitraClip device, compared to a clinical success rate of 73.0 percent for surgery patients (p=0.0007). The clinical success rate is defined as freedom from death, from surgery for valve dysfunction, and from moderate to severe MR (3+ or 4+).
In The New England Journal of Medicine, the study authors, who represent a variety of specialties including cardiac surgery and interventional cardiology, state that “although percutaneous repair was less effective at reducing mitral regurgitation than surgery before hospital discharge, at 12 and 24 months the rates of reduction in mitral regurgitation were similar, and percutaneous treatment was associated with increased safety, improved left ventricular dimensions, and clinical improvements in NYHA class and quality of life.”
“These results reinforce that the MitraClip device continues to be effective out to two years, confirming the durability of the clinical benefit and the safety profile of the therapy. Surgery also performed well in the trial,” 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, Ill. “The MitraClip system offers an option that addresses the unmet need for a percutaneous approach to treating MR, which may be especially important for many patients who are considered high-risk surgical candidates.”
Dr. Feldman served as co-principal investigator of the EVEREST II trial, was the lead author of The New England Journal of Medicine publication, and presented the two-year EVEREST II data during the late-breaking clinical trial session at ACC.
“In the EVEREST II study, the MitraClip device demonstrated strong safety and meaningful clinical benefits,” said Donald Glower, M.D., professor of surgery, Cardiovascular and Thoracic Surgery Division, Duke University School of Medicine, Durham, N.C., co-principal investigator of the EVEREST II trial and an author of The New England Journal of Medicine publication. “The MitraClip system’s positive risk-benefit profile supports its use as a treatment choice for patients who are not good candidates for surgery and have few other options, including elderly or frail patients, those who are at high risk for surgery, and certain patients with functional MR.”
The MitraClip system includes a catheter-based device that is delivered to the heart through the femoral vein, a blood vessel in the leg. The MitraClip therapy is designed to reduce significant MR by clipping together the leaflets of the mitral valve, one of the four valves of the heart.
The most common type of heart valve insufficiency,1 MR affects more than 4 million people in the United States – a prevalence of 11.7 percent of those aged 75 years and older.2 Significant MR is a debilitating condition in which the heart’s ability to function continues to deteriorate over time and may lead to irregular heartbeats, heart failure, stroke, heart attack or death. The condition traditionally has been managed with medications (which can relieve symptoms but do not address the underlying cause of the condition) or open-heart surgery. Many people who suffer from MR are not treated surgically3 because they are not referred to surgery, are not sick enough, or are too frail for an invasive procedure.
EVEREST II Data Demonstrate Durability Through Two Years
The EVEREST II pivotal trial is a multi-center, randomized clinical trial of 279 patients in the United States and Canada with moderate-to-severe (3+) or severe (4+) MR who were candidates for mitral valve surgery.
In addition to the clinical success rate at one and two years, data from the EVEREST II study showed the following on an ITT basis:
· At 30 days, the MitraClip system demonstrated superior safety compared to surgery, with 15.0 percent of MitraClip patients and 47.9 percent of surgery patients experiencing a major adverse event (MAE) (p<0.001). Major adverse events are defined as a composite of 12 pre-specified adverse events.
· At one and two years, both the MitraClip and surgery groups experienced a significant reduction (p<0.05) in the end systolic and end diastolic volume of the left ventricle heart chamber compared to baseline, indicating an improvement in heart function. In both groups, the decrease in end diastolic volume that was observed between baseline and one year continued to decrease between years one and two.
· Both the MitraClip device and surgery experienced a statistically significant reduction in New York Heart Association (NYHA) Functional Class symptoms at one year that was sustained through two years. NYHA Functional Class provides a scale that assists in the determination of functional ability in patients with heart disease.
· At two years, 78 percent of patients randomized to the MitraClip device were free from surgery.
· Longer-term follow-up of patients in EVEREST II is planned and will provide additional data to better understand the benefits of the MitraClip device.
· Two-year results from patients with functional MR and patients considered at high risk for mitral valve surgery were also featured in presentations at ACC. Results from both presentations demonstrated that positive one-year clinical outcomes were sustained out to two years.
“The publication of the EVEREST II data in The New England Journal of Medicine and today’s data presentation at ACC represent significant milestones in a nearly decade-long effort to develop a new treatment option for patients with mitral regurgitation,” said Charles A. Simonton, M.D., FACC, FSCAI, divisional vice president, Medical Affairs, and chief medical officer, Abbott Vascular. “Nearly 3,000 patients around the world have now been treated with the MitraClip device. We look forward to an FDA Advisory Panel to review the safety and effectiveness of the MitraClip device this year, hopefully bringing the technology a step closer to being available to U.S. physicians and patients.”
About Mitral Regurgitation (MR)
MR 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 (the main pumping chamber of the heart) to accommodate the increase in the volume of blood it is pumping. The chronic volume overload caused by MR requires the heart to work harder and may ultimately lead to heart failure and other complications. MR traditionally has been managed with drugs or open-heart surgery, depending on an individual patient’s severity of MR and risk factors.
About the MitraClip Technology and Procedure
Abbott’s proprietary MitraClip system is designed to reduce significant MR by clipping together the leaflets of the mitral valve, one of the four valves of the heart. The catheter-based MitraClip device is delivered to the heart through the femoral vein, a blood vessel in the leg. The heart beats normally during the procedure, and therefore does not require a heart-lung bypass machine. After treatment, patients are usually home within two to three days and have been observed to recover quickly. The safety and efficacy of the MitraClip system were evaluated in EVEREST II, a study supported by Abbott.
The MitraClip system received CE Mark in March 2008 and is commercially available in Europe, Turkey, Israel and Australia. The first-in-man clinical trial of the MitraClip system was conducted in the United States, where it is an investigational device currently under review for approval by the U.S. Food and Drug Administration.
About Abbott Vascular
Abbott Vascular is a global leader in cardiac and vascular care with market-leading products and an industry-leading pipeline. Abbott Vascular offers a comprehensive cardiac and vascular devices portfolio, including products for coronary artery disease, vessel closure, endovascular disease, and structural heart disease.
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs nearly 90,000 people and markets its products in more than 130 countries.
Abbott’s news releases and other information are available on the company’s Web site at www.abbott.com.
1 Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006 Sep 16; 368(9540):1005-11.
3 Bach DS, Awais M, Gurm HS, et al. Failure of guideline adherence for intervention in patients with severe mitral regurgitation. J Am Coll Cardiol 2009; 54:860-865.