Effect of Mechanically Expanded vs Self-Expanding Transcatheter Aortic Valve Replacement on Mortality and Major Adverse Clinical Events in High-Risk Patients With Aortic Stenosis: The REPRISE III Randomized Clinical Trial

Abstract

Importance: Transcatheter aortic valve replacement (TAVR) is established for selected patients with severe aortic stenosis. However, limitations such as suboptimal deployment, conduction disturbances, and paravalvular leak occur.

Objective: To evaluate if a mechanically expanded valve (MEV) is noninferior to an approved self-expanding valve (SEV) in high-risk patients with aortic stenosis undergoing TAVR.

Design, setting, and participants: The REPRISE III trial was conducted in 912 patients with high or extreme risk and severe, symptomatic aortic stenosis at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015, with final follow-up on March 8, 2017.

Interventions: Participants were randomized in a 2:1 ratio to receive either an MEV (n = 607) or an SEV (n = 305).

Main outcomes and measures: The primary safety end point was the 30-day composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications tested for noninferiority (margin, 10.5%). The primary effectiveness end point was the 1-year composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak tested for noninferiority (margin, 9.5%). If noninferiority criteria were met, the secondary end point of 1-year moderate or greater paravalvular leak was tested for superiority in the full analysis data set.

Results: Among 912 randomized patients (mean age, 82.8 [SD, 7.3] years; 463 [51%] women; predicted risk of mortality, 6.8%), 874 (96%) were evaluable at 1 year. The primary safety composite end point at 30 days occurred in 20.3% of MEV patients and 17.2% of SEV patients (difference, 3.1%; Farrington-Manning 97.5% CI, -∞ to 8.3%; P = .003 for noninferiority). At 1 year, the primary effectiveness composite end point occurred in 15.4% with the MEV and 25.5% with the SEV (difference, -10.1%; Farrington-Manning 97.5% CI, -∞ to -4.4%; P<.001 for noninferiority). The 1-year rates of moderate or severe paravalvular leak were 0.9% for the MEV and 6.8% for the SEV (difference, -6.1%; 95% CI, -9.6% to -2.6%; P < .001). The superiority analysis for primary effectiveness was statistically significant (difference, -10.2%; 95% CI, -16.3% to -4.0%; P < .001). The MEV had higher rates of new pacemaker implants (35.5% vs 19.6%; P < .001) and valve thrombosis (1.5% vs 0%) but lower rates of repeat procedures (0.2% vs 2.0%), valve-in-valve deployments (0% vs 3.7%), and valve malpositioning (0% vs 2.7%).

Conclusions and relevance: Among high-risk patients with aortic stenosis, use of the MEV compared with the SEV did not result in inferior outcomes for the primary safety end point or the primary effectiveness end point. These findings suggest that the MEV may be a useful addition for TAVR in high-risk patients.

Trial registration: ClinicalTrials.gov Identifier: NCT02202434.

Figure 1.. Patient Flow in the REPRISE III Randomized Clinical Trial

VARC indicates Valve Academic Research Consortium; PVL, paravalvular leak. ^aNo additional information is available. ^bThe clinical review committee was responsible for the review of patient screening data to confirm eligibility given the increased surgical risk of the patient population being studied and to ensure consistency of patients enrolled across study centers; 24 patients had aortic structures that were too large, 12 patients had aortic structures that were too small, 12 patients had peripheral vessels that were too small, and the rest were a mix of patients who had bicuspid valve, had excessive aortic tortuosity, or did not meet the risk criteria. ^cPatients who crossed over were included in the full analysis data set but were not included in the implanted analysis data set; the implanted patient population was the prespecified analysis population for noninferiority testing and includes all patients who signed an informed consent form, were enrolled in the trial, and underwent implantation of the study device they were randomized to receive (excludes crossover patients). Event rates were calculated after the index procedure. Patients who withdrew consent were included in the denominator if they had an event before withdrawal of consent. ^dSee Methods section of text for end-point definitions.

Figure 2.. Kaplan-Meier Time-to-Event Curves in the Full Analysis Data Set

HR indicates hazard ratio; MEV, mechanically expanded valve; SEV, self-expanding valve. The primary safety end point was a composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications through 30 days in the patient population undergoing implantation of the device they were randomized to receive. Median follow-up for the MEV group was 365 days (interquartile range, 369-391 days) and for the SEV group was 365 days (interquartile range, 346-387 days).