Early Clinical Outcomes With Evolut R Reassure, Suggest Improvements Over First-Gen CoreValve

Two new publications shed light on the early clinical outcomes of patients treated with the next-generation self-expanding Evolut R transcatheter aortic valve replacement device (Medtronic), with both analyses reporting similar rates of all-cause mortality and stroke at 30 days.

In the first study, Jeffrey Popma, MD (Beth Israel Deaconess Medical Center, Boston, MA) and colleagues report early clinical outcomes of 241 patients deemed “suboptimal” candidates for aortic-valve surgery participating in the CoreValve Evolut R US Clinical Study. At 30 days, the rates of all-cause mortality and disabling stroke were 2.5% and 3.3%, respectively. Life-threatening or disabling bleeding occurred in 7.1% of patients.

In the second study, a real-world analysis of 264 consecutive patients participating in the UK and Ireland Evolut R Implanters’ Registry, the survival rate at 30 days was 97.7%. Stroke--all non-disabling—occurred in 3.8% of patients. In the registry, 14.7% of patients required a new permanent pacemaker, which was implanted a median of 3 days after the procedure, compared with 16.4% of patients in the US clinical trial.

The rates of paravalvular leak were slightly higher in the UK/Ireland registry, with investigators reporting moderate or severe leak in 7.7% of patients. In the US Evolut R study, moderate paravalvular leak was documented in 5.3% of cases (there were no severe cases).  

Stephen Brecker, MD (St. George’s University Hospitals NHS Foundation Trust, London, UK), senior investigator of the UK/Ireland registry, told TCTMD that the rate of paravalvular leak classified as more serious than  mild occurred a little more frequently in their registry than what has been reported in clinical trials testing Evolut R. While it’s in the “same ballpark,” the characteristics of the real-world cohort are the likely explanation.  

“The baseline patient characteristics were broadly similar [to] other TAVR registries, but we had a few more patients treated for mixed aortic valve disease and we also included patients with a failing surgical aortic valve bioprostheses, which none of the other registries did,” he said. “Also, a large proportion of patients were treated emergently as inpatients. They weren’t elective, with routine work-up and culled admissions. Some of these patients were in the hospital in a pretty bad way and received a valve during that admission.”

Tamim Nazif (Columbia University Medical Center, New York, NY), who was not involved in either analysis, told TCTMD the 30-day results are a reflection of important iterative improvements over the original CoreValve and that they are equivalent, and in many instances better, than those reported with the predicate device. These data suggest physicians can use the valve safely as a workhorse, second-generation device, and that “it’s a standard of care that would be acceptable in the community,” he said.

Both studies are published online February 6, 2017 in JACC: Cardiovascular Interventions.

Registry Reflects Real-World Practice

The Evolut R is a recapturable and repositionable valve implanted through a 14-F compatible delivery system and is currently approved in the US and Europe. In the US clinical trial, the majority of patients were treated with the 29-mm valve, 35.0% with the 26-mm valve, and 1.3% with the 23-mm valve. In the UK/Ireland registry, 18.2% received the smallest valve, while 28.8% and 53.0% of patients were treated with the 26-mm and 29-mm valves. No patients in either study received the 34-mm valve, a device only recently approved in the US and Europe.  

Brecker said their patients reflect clinical practice after device approval. “It’s a typical high-risk population, although not extreme risk,” he said. “The patients were not all inoperable. Some of the patients would have been inoperable, and while some would have been high risk for surgery, frankly, some of the patients would have been considered intermediate- or low-risk [for surgery]. It reflects real-world practice outside of the constraints of the clinical trial.”

In the registry, the average age of patients receiving the Evolut R device was 81 years old and the mean EuroSCORE was 19.9. Overall, the procedural success rate was 91.3%, with nearly 95% treated with transfemoral access. Approximately 40% of patients were treated with conscious sedation. The overall rate of major vascular complications was 5.3%.

Comparatively, in the US clinical trial, patients were 83.3 years old and had an STS score of 7.4. Transfemoral access was performed in 89.5% of cases and just one in five patients was treated with conscious sedation. The rate of vascular access-site complications was 7.5%.   

Brecker said the rate of permanent pacemaker implantation was “quite low,” despite 24% of patients having conduction disease prior to implantation. Overall, 7.2% of patients had a pre-existing pacemaker prior to TAVR. “I think we are learning that pacing is still an issue,” said Brecker. “It’s an issue with all the valves, although it’s less of an issue with Evolut R than with the first-generation self-expanding valve.”

In an editorial accompanying the study, Marco Barbanti, MD (University of Catania, Italy), points out that the observed rates of permanent pacemaker implantation with Evolut R were rarely that low with the first-generation CoreValve device. Additionally, the lower rates of paravalvular leak also represent a “non-negligible” step forward compared with the older device. 

“However, these results cannot be considered completely satisfying,” he writes. “This is particularly true in an era in which TAVR is being progressively offered to younger and lower-risk patients, and the paravalvular leak rate is approximately 1% to 2% with some new-generation transcatheter aortic valves.”

Device Improvements Translate Into Benefit

For Nazif, the low rate of vascular complications is the result of the smaller 14-F delivery system, and to some extent, improvements in technique among operators. The high rate of pacemaker implantation with CoreValve—in the order of 25% with the first-generation device—was a “handicap,” the device’s “Achilles heel.” Both the US trial and UK/Irish registry reflect dramatic improvements, however, bringing the pacemaker implantation rate much closer to results observed with the balloon-expandable valve. 

Regarding the rate of stroke and all-cause mortality, Nazif said these are also quite favorable and low compared with earlier TAVR trials and reports, although perhaps quite not as “breathtaking” as some reports with Sapien 3, the next-generation device manufactured by Edwards Lifesciences. But, he added, comparing different registries and trials remains challenging, and unfair, particularly since there are differences in baseline patient characteristics and comorbidities.

On the whole, the new data with Evolut R provide “complementary evidence that this second-generation device has real, practical advantages relative to the first-generation device that improve patient outcomes in a measurable fashion,” said Nazif. “And I think that’s important, and is exactly the type of thing you’d hope to see in this data.”

For Brecker, the Evolut R is a “user-friendly device” and they plan to expand the registry to assess performance of the 34-mm valve now that it is commercially available. In addition, they will include patients treated with the Evolut R PRO system, which is a still investigational next-generation system with a porcine pericardial skirt.

“We always want smaller valve delivery systems and we want as close to zero rates of paravalvular leaks and pacing as possible,” said Brecker. “My sense is that we have a ways to go on all the currently available valves in achieving that dual goal.”

In his editorial, Barbanti makes a similar argument, stating there is still room for technological improvement. While the outcomes are “exceptional,” he urges continued disruption to improve and refine the technology. 

Photo Credit: Medtronic (adapted from http://www.corevalve.com/us/product/index.htm)