US Pivotal Trial Shows Medtronic's CoreValve TAVR System Is Superior to Surgery in High-Risk Patients at 1 Year

March 29, 2014—Medtronic, Inc. (Minneapolis, MN) announced that the company’s CoreValve system for transcatheter aortic valve replacement (TAVR) showed results that are superior to surgical aortic valve replacement (SAVR) at 1 year in the High Risk Study of its CoreValve United States Pivotal trial, which evaluated patients with severe aortic stenosis who are considered high risk for surgery. 

The data were presented at a late-breaking clinical trial session at the ACC.14: 63rd annual scientific session of the American College of Cardiology and simultaneously published online ahead of print by David H. Adams, MD, et al in The New England Journal of Medicine.

In January 2014, Medtronic announced that the CoreValve system was approved by the US Food and Drug Administration (FDA) for patients considered extreme risk for surgery. The device is not currently approved in the United States for use in patients at high risk, advised Medtronic. The CoreValve system received European CE Mark approval in 2007. 

As summarized by Medtronic, the head-to-head study met its primary endpoint with a 1-year all-cause mortality rate of 14.2% in patients undergoing CoreValve placement versus 19.1% in patients undergoing SAVR at 1 year (noninferiority P-value < .001; superiority P-value = .04). 

Dr. Adams, who presented the data at ACC.14 and serves as the National Coprincipal Investigator of the CoreValve United States Pivotal trial, commented in Medtronic’s press release, “The extremely low mortality rates in both arms of the trial confirm that our heart teams were outstanding, particularly considering they had no prior experience with transcatheter aortic valve therapy. Our key finding that TAVR with CoreValve was associated with a significantly higher rate of survival at 1 year in patients at increased risk has significant and broad implications.” Dr. Adams is Chair of the Department of Cardiothoracic Surgery at the Mount Sinai Hospital in New York, New York

Medtronic noted that stroke rates in patients with the CoreValve system were low and not statistically different than in SAVR patients. As determined by detailed neurological assessments before and after each procedure, major stroke rates in patients who underwent CoreValve TAVR placement were 3.9% at 30 days and 5.8% at 1 year compared with the rates in patients who underwent SAVR of 3.1% at 30 days and 7% at 1 year.  

Additionally, CoreValve patients experienced significant improvements in their quality of life. These scores improved 19 points for CoreValve TAVR patients and 3.7 points for SAVR patients at 30 days (P ≤ .0001). At 1 year, both patient groups improved significantly, with CoreValve patients improving by 23.2 points and surgical patients improving by 21.9 points (as measured by KCCQ 100-point scale, in which 5 points is considered important, and 20 points is considered a very large improvement).

The trial’s national Coprincipal Investigator Jeffrey J. Popma, MD, commented in Medtronic’s announcement, “The results of the High Risk study confirm our findings in the Extreme Risk study, namely that careful preprocedural planning with CT-based determination of valve sizing and attention to ‘best practice’ implantation techniques result in a strong hemodynamic performance of the self-expanding CoreValve with low rates of 1-year paravalvular regurgitation and stroke.” Dr. Popma is Director of Interventional Cardiology at the Beth Israel Deaconess Medical Center in Boston, Massachusetts.

Medtronic further noted that although there was no statistical difference between CoreValve TAVR system and SAVR in rates of major adverse cardiovascular or cerebral events (MACCE) at 30 days (P = .1), at 1 year, the MACCE rate was significantly better for CoreValve patients (P = .03). The frequency of death or major stroke at 1 year was also lower with CoreValve (P = .03). Overall hemodynamic performance in CoreValve patients was better than SAVR across all time points (P ≤ .02 at discharge, 30 days, and 1 year). In addition, rates of moderate or severe paravalvular leak for TAVR were acceptably low, with 7.8% at discharge and 6.1% at 1 year. Consistent with the Extreme Risk study, paravalvular leak in most patients improved over time. As with previous studies on self-expanding technology, the permanent pacemaker rate was 19.8% at 1 month and, importantly, a difference in mortality was not observed for these patients, stated Medtronic.

In related news, Medtronic advised that after reviewing the CoreValve trial’s results for high-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.