Data Presented on MitraClip for Treating High Risk and Elderly Patients

May 5, 2011—The Society for Cardiovascular Angiography and Interventions (SCAI) announced that the MitraClip system (Abbott Vascular, Santa Clara, CA) is showing consistent performance in three analyses of its safety and effectiveness in high-risk patients, which were presented at the 2011 SCAI scientific sessions in Baltimore, Maryland. A separate study shows that even elderly high-risk patients enjoy a significant and long-lasting improvement in quality of life after treatment with the catheter-based procedure.

The four studies are: 

• “EVEREST II REALISM: a continued access study to evaluate the safety and effectiveness of the MitraClip device: analysis of a 6-month patient cohort,” presented by Michael Rinaldi, MD, in an oral abstract session
• “EVEREST II REALISM: a continued access study to evaluate the safety and effectiveness of the MitraClip device: demographics and procedural outcomes,” presented by Saibal Kar, MD, in a poster session 
• “Quality of life of high-risk patients following percutaneous mitral valve repair with the MitraClip system,” presented by Kunal Sarkar, MD, in a poster session
• “Transcatheter mitral valve repair versus surgery in the elderly,” presented by Scott Lim, MD, in a poster session

Data for the first two studies come from the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) high-risk clinical trial of the MitraClip system and/or EVEREST II REALISM (Real World Expanded Multicenter Study of the MitraClip System), a prospective continued-access study designed to collect data on the “real-world” use of the MitraClip system in the United States. Quality-of-life data for the third study are drawn from patients who were treated at the University of Catania in Italy, where the MitraClip system is commercially available. 

The EVEREST II randomized clinical trial previously showed that repairing the mitral valve using the MitraClip system is safe and results in clinical outcomes are similar to those of surgery. As reported in Cardiac Interventions Today, 2-year EVEREST II data showing the durable clinical benefits of the system were presented on April 4 by Co-principal Investigator Ted Feldman, MD, at the American College of Cardiology's annual scientific session in New Orleans. 

In the United States, the MitraClip system is an investigational device that is currently under review for approval by the US Food and Drug Administration. The device received CE Mark in March 2008 and is commercially available in Europe, Turkey, Israel, and Australia.

EVEREST II REALISM: Analysis of a 6-Month Patient Cohort

According to SCAI, Dr. Rinaldi led an analysis comparing procedural safety at 30 days and clinical outcomes at 12 months in two groups of patients who were judged to be at high risk for surgery: 133 enrolled in the EVEREST II REALISM continued-access study and 78 from the EVEREST II high-risk clinical trial. The investigators found that initial results were consistent when comparing the two groups of patients. The MitraClip procedure was found to be safe, with a 30-day mortality rate of 3.8% in the continued-access study group and 7.7% in the high-risk group (P = .34).

The investigators also evaluated longer-term clinical outcomes in patients with matched data both at the beginning of the study and at 12 months. The reduction in the amount of blood leaking through the mitral valve was consistent across both groups. In the EVEREST II REALISM continued-access study, 83% of high-risk patients had only mild-to-moderate mitral regurgitation (MR) (grade 1+ or 2+) at 1 year compared with 78% of patients in the EVEREST II high-risk trial. Patients in both groups experienced additional clinical benefits, including significant improvements in the function of the left ventricle and in their ability to engage in day-to-day activities, as gauged by New York Heart Association (NYHA) functional class. The rate of rehospitalization for congestive heart failure was also significantly lower during the 12 months after treatment when compared with the 12 months before treatment, with an average reduction of 47%.

SCAI noted that an important difference between the two sets of patients was physician experience with the MitraClip procedure. The 25 interventionists who enrolled high-risk patients in the EVEREST II clinical trial had experience performing an average of 10 procedures. In EVEREST II REALISM, the 34 interventionists had experience performing an average of 23 procedures.

The investigators observed that procedural safety improved with increased physician experience. For example, procedure time was significantly shorter in the EVEREST II REALISM continued-access study (153 minutes on average vs 190 minutes in the EVEREST II high-risk clinical trial; P < .001), as was postprocedure time in the intensive care unit (25 hours for patients in the continued-access study vs 52 hours for patients in the high-risk clinical trial; P = .005). Hospital stay was also significantly shorter (2.5 days on average vs 3.9 days, respectively; P = .05).

“The continued-access results demonstrate that for patients who might not do well with surgery, not only is the MitraClip procedure successful, but results are improving over time with increased operator experience—including shorter procedure times, shorter hospital stays, and reduced 30-day mortality,” stated Dr. Rinaldi. “This suggests that the MitraClip therapy is an option for this group and has the potential to meet an unmet clinical need.”

EVEREST II REALISM: Demographics and Procedural Outcomes

In Dr. Kar’s analysis of demographic data from EVEREST II REALISM, the average age of patients enrolled in the study was younger than 70 years. Before the MitraClip procedure, 84% of patients in the high-risk group and 50% of patients in a separate “usual-risk” group had marked limitations in their ability to walk or even get out of bed (NYHA class III or IV). Approximately 75% of high-risk patients and 40% of usual-risk patients had a functional MR, which is harder to repair even with surgery than degenerative MR and results from valve flaps that are scarred or defective.

In the third study, which was focused on quality of life, investigators recruited 49 elderly patients who, on average, would have had a 20% risk of dying during or shortly after open-chest surgery. Approximately 77% of patients were in NYHA class III or IV. Two-thirds had functional MR.

Quality of Life in High-Risk Patients

Dr. Sarkar reported that the MitraClip procedure was successful in all patients, with a significant reduction in MR to no more than a mild-to-moderate level. At 6-month follow-up, all patients were in NYHA class I. In addition, the investigators observed improvements in quality of life. Scores for physical well being climbed from 35 on average to 44 (P < .0001), and scores for mental well being went from 38 on average to 46 (P = .0001). Patients with functional MR had worse quality-of-life scores before the MitraClip procedure when compared to patients with degenerative MR, but they experienced a greater improvement after the procedure.

“The 6-month improvement in quality of life was more than we expected, especially for patients with functional MR,” stated Dr. Sarkar. “These findings provide the basis for future, larger studies with longer follow-up to identify patient subpopulations who would stand to gain maximum benefit from the MitraClip procedure.”

MitraClip Treatment in the Elderly

According to SCAI, Dr. Lim’s presentation shows that the MitraClip is not only safer over the short term than surgery in elderly patients, but also its effectiveness remains evident even 2 years after the procedure. Data from the EVEREST studies show that in patients 70 years of age or older, use of the MitraClip to treat a leaky mitral valve significantly reduces procedure-related complications during the first 30 days when compared to surgery. In addition, during longer follow-up, the safety and effectiveness of the MitraClip was found to be noninferior to the standard surgical approach.

“Elderly patients are less-than-ideal candidates for open-heart surgery,” commented Dr. Lim. “This is the first time we’ve really looked at an older group of patients and asked, ‘Does the MitraClip procedure have a role for them?’ I think the answer is yes.”

The investigators analyzed data from the EVEREST I, EVEREST II, and EVEREST II REALISM studies on 118 patients aged 70 years and older. Of these, 84 were treated with the MitraClip and 34 had surgery.

The primary aim of the study was to compare the safety of the two procedures. At 30 days, the rate of major adverse events (including death, stroke, need for blood transfusion, prolonged stay in the intensive care unit, or need for additional surgery) was significantly lower in patients treated with the MitraClip compared to surgery (17.9% vs 73.5%; P < .0001). When the need for transfusion was eliminated from the analysis, the 30-day event rates were 7.1% and 14.7%, respectively, a difference that was not statistically significant.

At 12-month follow-up, the combined rates of survival, acceptable levels of MR, and avoidance of new mitral valve surgery were 72.2% among patients treated with the MitraClip and 76.7% among patients treated with surgery. At 24-month follow-up, the rates were 63.9% and 70%, respectively.

The investigators found that surgery appeared to be significantly better than the MitraClip at reducing MR. At 12 months, 86.8% of patients treated with the MitraClip and 95.8% of patients who underwent surgery had no more than mild-to-moderate MR (P = .02), a finding that was still evident at 24 months. Dr. Lim speculated that this observation may reflect differences in how MR appears on echocardiography after the two procedures, rather than a shortcoming of the MitraClip procedure. He noted that if surgery actually improved MR to a greater degree than the MitraClip, there should be a greater reduction in heart size in the surgery group. However, at 12 and 24 months, the volume of the left ventricle was significantly smaller in both groups, with no significant difference between the MitraClip and surgery groups.

The investigators also found that patients treated with the MitraClip did significantly better when it came to performing everyday activities, even long after a full recovery would be expected among surgery patients. At 12 months, 97.1% of MitraClip patients and 75% of surgery patients were classified as being in NYHA functional class I or II, experiencing little or no functional impairment (P = .0007); at 24 months, those rates were 98.2% and 84%, respectively.

“With any new therapy, there’s always a balance between safety and efficacy,” concluded Dr. Lim. “These data show that, particularly in older patients, the MitraClip is a very attractive option given its excellent safety and acceptable efficacy.”