CoreValve system results superior to open-heart surgery at one year in US pivotal trial

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Medtronic announced that the CoreValve system showed results superior to surgical aortic valve replacement (SAVR) at one year in the High Risk Study of its CoreValve US 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 63rd Annual Scientific Session of the American College of Cardiology (ACC) and simultaneously published in The New England Journal of Medicine.

The head-to-head study met its primary endpoint with a low one year, all-cause mortality rate of only 14.2% in patients receiving the CoreValve system, compared to 19.1% in patients receiving SAVR at one year (non-inferiority p-value<0.001; superiority p-value=0.04). The CoreValve High Risk Study is the first prospective, randomised study to show any transcatheter aortic valve to be superior to surgery.

“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,” says David H Adams, chair of the Department of Cardiothoracic Surgery at the Mount Sinai Hospital, New York City, USA, national co-principal investigator of the CoreValve US Pivotal Trial and presenter of the data at ACC. “Our key finding that TAVR with CoreValve was associated with a significantly higher rate of survival at one year in patients at increased risk has significant and broad implications.”

Stroke rates in patients with the CoreValve system were low and not statistically different than in SAVR patients; this finding is especially important because stroke is one of the complications most concerning to physicians and patients because it increases mortality and affects quality of life. As determined by detailed neurological assessments before and after each procedure, major stroke rates in patients who received the CoreValve system were 3.9% at 30 days and 5.8% at one year, while those same rates for patients with surgery were 3.1% (30 days) and 7% (one year). 

Patients also saw significant improvements in their quality of life. Quality of life scores improved 19.0 points for CoreValve patients and 3.7 points for surgical patients at 30 days (p=<0.0001); at one year both patient groups improved significantly with CoreValve patients improving 23.2 points and surgical patients improving 21.9 points (as measured by KCCQ 100-point scale, where five points is considered important, and 20 points is considered a very large improvement).

“The results of the High Risk study confirm our findings in the Extreme Risk Study, namely that careful pre-procedural planning with CT-based determination of valve sizing and attention to ‘best practice’ implantation techniques result in a strong haemodynamic performance of the self-expanding CoreValve with low rates of one year paravalvular regurgitation and stroke,” says Jeffrey J Popma, director of Interventional Cardiology at the Beth Israel Deaconess Medical Center, Boston, USA, and national co-principal investigator of the CoreValve US Pivotal Trial.

While there was no statistical difference between CoreValve system and surgery in MACCE (major adverse cardiovascular or cerebral events) rates at 30 days (p=0.1), at one year the MACCE rate was significantly better for CoreValve patients (p=0.03). The frequency of death or major stroke at one year was also lower with CoreValve (p=0.03). Overall haemodynamic (blood flow) performance in CoreValve patients was better than SAVR across all time points (p=<0.02 at discharge, 30 days and one year). In addition, rates of moderate or severe paravalvular leak for TAVR were acceptably low with 7.8% at discharge and 6.1% at one 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 one month and, importantly, for these patients a difference in mortality was not observed.

The CoreValve System was approved by the US Food and Drug Administration (FDA) in January 2014 for patients considered extreme risk for surgery; the device is not currently approved in the USA for use with patients at high risk. Since receiving CE (Conformité Européenne) mark in 2007, the CoreValve System has been implanted in more than 50,000 patients in more than 60 countries.

Upon 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.