Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System – Randomized Clinical Evaluation - REPRISE III

Mar 01, 2019
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Boston Scientific
Date Presented:
03/12/2018
Date Published:
02/27/2019
Date Updated:
03/01/2019
Original Posted Date:
03/12/2018
References

Contribution To Literature:

The REPRISE III trial showed that the mechanically expanding Lotus valve is noninferior to the self-expanding CoreValve for the safety and efficacy endpoints at 1 year among high- and extreme-risk aortic stenosis patients undergoing TAVR.

Description:

The goal of the trial was to compare the safety and efficacy of Boston Scientific’s Lotus valve to Medtronic’s CoreValve among patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis.

Study Design

Patients undergoing TAVR were randomized in a 2:1 fashion to either TAVR with the Lotus Valve (n = 607) or the CoreValve (n = 305).

  • Total screened: 1,232
  • Total number of enrollees: 912
  • Duration of follow-up: 12 months
  • Mean patient age: 82.9 years
  • Percentage female: 51%

Inclusion criteria:

  • Symptomatic severe native AS with a valve area of ≤1.0 cm2 (or an aortic valve area [AVA] index ≤0.6 cm2/m2) and a mean pressure gradient of ≥40 mm Hg or a jet velocity of ≥4.0 m/s
  • Society of Thoracic Surgeons Predicted Risk of Mortality score (STS-PROM) ≥8% or another indicator of high or extreme surgical risk
  • Agreement among local heart team regarding risk and suitability for TAVR
  • An aortic annulus size of ≥20 mm and ≤27 mm (based on computed tomography) and eligibility for an available size of both valves

Exclusion criteria:

  • Uni- or bicuspid aortic valve
  • Acute myocardial infarction within 30 days or cerebrovascular accident within 6 months
  • End-stage renal disease or glomerular filtration rate <20
  • Pre-existing prosthetic heart aortic or mitral valve
  • Severe aortic regurgitation, mitral regurgitation, tricuspid regurgitation
  • Emergent procedure
  • History or current endocarditis

Other salient features/characteristics:

  • Extreme risk: 23%
  • Mean STS-PROM 6.8, ≥8%: 30%

Principal Findings:

The primary safety outcome, composite of all-cause mortality, stroke, life-threatening and major bleeding, stage 2/3 acute kidney injury, and major vascular complications at 30 days, for Lotus vs. CoreValve, was 20.3% vs. 17.2%, p for noninferiority = 0.003, p for superiority = 0.83.

The primary efficacy outcome, all-cause mortality, disabling stroke, and moderate or greater paravalvular aortic regurgitation through 1 year, was 15.4% vs. 25.5%, p < 0.001.

Secondary outcomes (Lotus vs. CoreValve):

  • Moderate to severe paravalvular leak (PVL) at 1 year: 0.9% vs. 6.9%, p < 0.001
  • All-cause mortality: 11.9% vs. 13.5%, p = 0.48
  • Stroke: 7.0% vs. 9.4%
  • Permanent pacemaker (PPM): 34.2% vs. 18.5%, p < 0.05
  • Prosthetic TAVR valve thrombosis: 1.5% vs. 0%. All but one of these occurred in the 23 mm valve.

Hemodynamic performance: At discharge, mean gradient was higher for the Lotus valve compared with CoreValve (12.3 vs. 8.2 mm Hg, p < 0.001), AVA was lower (1.64 vs. 1.96 cm2, p < 0.001). Between discharge and 1 year, change in mean gradient at 1 year was similar among the two groups. The AVA (-0.16 vs. -0.27) decreased significantly more in CoreValve than Lotus patients, although the difference remained higher at all time-points for CoreValve.

Two-year results (Lotus vs. CoreValve):

  • All-cause mortality: 21.3% with Lotus vs. 22.5% with CoreValve, hazard ratio 0.94, 95% confidence interval 0.69-1.26, p = 0.67
  • All strokes: 8.4% vs. 11.4%, p = 0.21; disabling stroke: 4.7% vs. 8.6%, p = 0.02; valve thrombosis: 3.0% vs. 0%, p < 0.01, mean gradient: 13.0 vs. 8.1 mm Hg, p < 0.01; AVA 1.53 vs. 1.76 cm2, p < 0.01; moderate/severe PVL: 0.3% vs. 3.8%, p < 0.01

Interpretation:

The results of this trial indicate that Boston Scientific’s mechanically expanding Lotus valve was noninferior to Medtronic’s self-expanding CoreValve for the safety and efficacy endpoints at 1 year among high- and extreme-risk aortic stenosis patients undergoing TAVR. Rates of moderate to severe PVL with Lotus were significantly lower up to 2 years, while PPM implantation rates were significantly higher. Also, effective orifice area (EOA) and mean gradient were better with the CoreValve (likely a function of its supra-annular design). In addition, the rate of valve thrombosis was higher with the Lotus valve (symptomatic in 25% of affected patients). This is an important trial, as it provides head-to-head comparison between TAVR valves.

Some points to consider: The CoreValve arm contained patients receiving both CoreValve Classic and Evolut valves. The latter is the second-generation valve and was specifically designed to reduce PPM and PVL rates (for instance, PVL rates with Evolut were 2.8% compared with 10.6% with CoreValve Classic). The Lotus valve is not yet commercially available in the United States, and similarly, CoreValve Classic was phased out in favor of the next-generation CoreValves in the United States.

References:

Reardon MJ, Feldman TE, Meduri CU, et al. Two-Year Outcomes After Transcatheter Aortic Valve Replacement With Mechanical vs Self-expanding Valves: The REPRISE III Randomized Clinical Trial. JAMA Cardiol 2019;Feb 27:[Epub ahead of print].

Asch FM, Vannan MA, Singh S, et al. Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk: An Analysis From the REPRISE III Randomized Controlled Trial (Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System - Randomized Clinical Evaluation). Circulation 2019;137:2557-67.

Feldman TE, Reardon MJ, Rajagopal V, et al. 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. JAMA 2018;319:27-37.

Poster presented by Dr. Federico Asch at the American College of Cardiology Annual Scientific Session (ACC 2018), Orlando, FL, March 12, 2018.

Keywords: ACC18, ACC Annual Scientific Session, Acute Kidney Injury, Aortic Valve Insufficiency, Aortic Valve Stenosis, Heart Valve Diseases, Heart Valve Prosthesis, Hemorrhage, Hemodynamics, Pacemaker, Artificial, Stroke, Thrombosis, Tomography, Transcatheter Aortic Valve Replacement


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