Medtronic’s CoreValve US Pivotal Trial Results Presented at TCT
October 29, 2013—Medtronic, Inc. (Minneapolis, MN) announced that coprincipal investigator Jeffrey J. Popma, MD, presented the results from the CoreValve United States pivotal trial at a late-breaking clinical trial session of the TCT 2013: Transcatheter Cardiovascular Therapeutics conference in San Francisco, California. These are the first United States data on Medtronic’s self-expanding CoreValve transcatheter aortic valve replacement (TAVR) system.
According to Medtronic's announcement, the trial met its primary endpoint for treatment with the CoreValve system in patients who were considered too ill or frail to undergo surgical aortic valve replacement, with a rate of death or major stroke at 1 year of 25.5%. The company stated that this result is highly significant (P < .0001) because it was 40.7% lower in patients treated with the CoreValve system than was expected with standard therapy, with a prespecified performance goal of 43%. At 1 month, the major stroke rate was 2.4%, and it remained low over time, with a 1-year rate of 4.1%. In addition, in more than 800 extreme-risk patients enrolled in the CoreValve continued-access study, CoreValve patients experienced an even lower rate of major stroke (1.8% at 1 month).
“The fact that nearly three-quarters of patients were alive and free of strokes at 1 year is remarkable, given the complex medical conditions and extreme frailty of this population," commented Dr. Popma in the press release. "Not only do the results meet the CoreValve study's safety and efficacy endpoints for patients at extreme risk for surgery, but the positive clinical outcomes and low complication rates set a high standard for what transcatheter valves can achieve.” Dr. Popma is Director of Interventional Cardiology at the Beth Israel Deaconess Medical Center in Boston, Massachusetts.
In the study, 471 patients were treated with the CoreValve system, a self-expanding, 18-F low-profile system with three valve sizes (26 mm, 29 mm, and 31 mm) delivered via the femoral artery. Patients were monitored by independent core labs and evaluated against a performance goal developed in partnership with the US Food and Drug Administration (FDA). In the CoreValve Continued Access Study, 830 extreme-risk patients have been treated with CoreValve system.
Medtronic reported that the study also found significant and sustained functional and quality-of-life improvements, with the heart failure symptoms of most patients (90%) improving at least one class at 1 year (as measured by NYHA class) and quality-of-life scores improving 27.4 points at 1 year (as measured by the KCCQ 100-point scale, in which a 20-point change is considered highly significant).
Overall hemodynamic performance was strong, with mean gradients of 8.5 mm Hg at 1 month and 8.8 mm Hg at 1 year, similar to surgical valves. Paravalvular leak (PVL) rates were low and improved over time; 11.5% of patients had more than mild PVL at 1 month, which improved to 4.1% at 1 year.
The company noted that more than 80% of patients with moderate PVL at 1 month had a reduction in the severity of PVL by 1 year, an improvement that has not been reported in other major TAVR trials. Additionally, CoreValve patients with moderate PVL had no greater mortality risk than patients with less PVL.
Medtronic also advised that major vascular complication rates were low: 8.3% at 1 month and 8.5% at 1 year. Consistent with previous studies on self-expanding technology, the permanent pacemaker rate was 22.2% at 1 month and, importantly, pacemaker implants were not associated with mortality for these patients.
Medtronic also provided an update on the FDA’s review of the CoreValve for approval in the United States. The FDA has determined it will conduct separate reviews for the CoreValve trial's extreme-risk and high-risk studies. From its review of the CoreValve trial's results for extreme-risk patients, the FDA has determined it has sufficient information to evaluate the safety and efficacy of the Medtronic CoreValve system for this patient group without the need for an external expert panel. Medtronic stated that the CoreValve system is currently not approved for commercial use in the United States and that the company anticipates receiving FDA approval of the device for extreme-risk patients by the end of its fiscal year 2014. The CoreValve system received European CE Mark approval in 2007.