The use of mechanically expandable valves was not inferior to self-expandable valves in high risk patients with severe aortic stenosis enrolled in the REPRISE III clinical trial. The trial results support the potential for the first generation LOTUS valve to become part of regular clinical practice.
“REPRISE III is the 1st large randomized direct comparison of two contemporary TAVR devices; mechanically expanded valve (MEV) and self-expandable valve (SEV)” according to Dr. Ted Feldman, who is the first author of the study that was recently published in the Journal of the American Medical Association (JAMA).
Dr. Michael Reardon, the surgical principal investigator of the REPRISE III trial added, “The LOTUS valve had already been tested in several out of the US trials. It was already known that the valve could be implanted safely with a very low rate of paravalvular leak (PVL).”
The REPRISE III trial was conducted at 55 centers in North America, Europe, and Australia from September 2014 to December 2015. A total of 912 patients with high risk, severe symptomatic aortic stenosis were randomized in a 2:1 ratio to receive either a MEV (n = 607) or a SEV (n = 305). The primary safety endpoint was the composite of all-cause mortality, stroke, life-threatening and major bleeding events, stage 2/3 acute kidney injury, and major vascular complications at 30 days. The primary effectiveness endpoint was the 1-year composite rate of all-cause mortality, disabling stroke, and moderate or greater PVL based on core laboratory assessment. The secondary end point was moderate or greater PVL at 1 year.
“The ability to completely deploy the valve and assess its function while still being able to recapture, reposition and redeploy if necessary. It is the only valve that can be recaptured at complete deployment.”-Dr. Michael Reardon
The REPRISE III trial demonstrated non-inferiority, for the primary safety and efficacy endpoints, of the first generation LOTUS valve (MEV) compared to the CoreValve (SEV). In addition, the MEV reduced the rate of moderate or severe PVL by 6%, demonstrating superiority over the SEV. When asked to comment, Dr. Reardon told Cardiology Now that “this is the first valve to use a sealing skirt to reduce PVL and has always shown a very low PVL rate which was confirmed in this trial.”
Additionally, no valve-in-valve deployments occurred with the MEV compared to 11 in the SEV arm. Dr. Reardon was not surprised by this finding because of “the ability to completely deploy the valve and assess its function while still being able to recapture, reposition and redeploy if necessary. It is the only valve that can be recaptured at complete deployment.”
Importantly, this trial revealed that the MEV had higher rates of new pacemaker implants and valve thrombosis compared to SEV. In the publication, the authors noted that “the findings of this study are consistent with a recent investigation that suggested that the supra-annular SEV may have a lower rate of valve thrombosis. Approaches to prevention, detection, and treatment of valve thrombosis are currently being studied.” In this study, none of the patients with valve thrombosis died or had a stroke. Dr. Feldman added that “the higher permanent pacemaker implant rate with the LOTUS valve should be addressed the next generation device.” However, “this will need to be tested in clinical trials.”
The authors acknowledged an important limitation. Balloon aortic valvuloplasty before dilatation was mandated by the study protocol. This procedure is no longer routine clinical practice.
When asked to comment on the implications of this study’s findings on clinical practice, Dr. Reardon told Cardiology Now News that “currently the [MEV] valve is on hold while an issue with the pin release mechanism is corrected. When this is corrected, as I am confident it will be, then this valve becomes the third major type of valve that can be used and each type have their strengths and weakness. We have balloon expandable, self-expanding and the LOTUS mechanically expanded valve. Having three different types of valve to choose from and match to the individual patient will be an advantage to particularly higher volume centers.”