Elsevier

The Lancet

Volume 394, Issue 10209, 2–8 November 2019, Pages 1619-1628
The Lancet

Articles
Safety and efficacy of a self-expanding versus a balloon-expandable bioprosthesis for transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis: a randomised non-inferiority trial

https://doi.org/10.1016/S0140-6736(19)32220-2Get rights and content

Summary

Background

Transcatheter aortic valve replacement (TAVR) is the preferred treatment option for older patients with symptomatic severe aortic stenosis. Differences in the properties of available TAVR systems can affect clinical outcomes. Among patients undergoing TAVR, we compared the self-expanding ACURATE neo TAVR system with the balloon-expandable SAPIEN 3 TAVR system with regard to early safety and efficacy.

Methods

In this randomised non-inferiority trial, patients (aged ≥75 years) undergoing transfemoral TAVR for treatment of symptomatic severe aortic stenosis, and who were deemed to be at increased surgical risk, were recruited at 20 tertiary heart valve centres in Germany, the Netherlands, Switzerland, and the UK. Participants were randomly assigned (1:1) to receive treatment with the ACURATE neo or the SAPIEN 3 with a computer-based randomly permuted block scheme, stratified by study centre and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) category. The primary composite safety and efficacy endpoint comprised all-cause death, any stroke, life-threatening or disabling bleeding, major vascular complications, coronary artery obstruction requiring intervention, acute kidney injury (stage 2 or 3), rehospitalisation for valve-related symptoms or congestive heart failure, valve-related dysfunction requiring repeat procedure, moderate or severe prosthetic valve regurgitation, or prosthetic valve stenosis within 30 days of the procedure. Endpoint assessors were masked to treatment allocation. Non-inferiority of ACURATE neo compared with SAPIEN 3 was assessed in the intention-to-treat population on the basis of a risk-difference margin of 7·7% for the primary composite endpoint, with a one-sided α of 0·05. This trial is registered with ClinicalTrials.gov (number NCT03011346) and is ongoing but not recruiting.

Findings

Between Feb 8, 2017, and Feb 2, 2019, up to 5132 patients were screened and 739 (mean age 82·8 years [SD 4·1]; median STS-PROM score 3·5% [IQR 2·6–5·0]) were enrolled. 30-day follow-up was available for 367 (99%) of 372 patients allocated to the ACURATE neo group, and 364 (99%) of 367 allocated to the SAPIEN 3 group. Within 30 days, the primary endpoint occurred in 87 (24%) patients in the ACURATE neo and in 60 (16%) in the SAPIEN 3 group; thus, non-inferiority of the ACURATE neo was not met (absolute risk difference 7·1% [upper 95% confidence limit 12·0%], p=0·42). Secondary analysis of the primary endpoint suggested superiority of the SAPIEN 3 device over the ACURATE neo device (95% CI for risk difference −1·3 to −12·9, p=0·0156). The ACURATE neo and SAPIEN 3 groups did not differ in incidence of all-cause death (nine patients [2%] vs three [1%]) and stroke (seven [2%] vs 11 [3%]); whereas acute kidney injury (11 [3%] vs three [1%]) and moderate or severe prosthetic aortic regurgitation (34 [9%] vs ten [3%]) were more common in the ACURATE neo group.

Interpretation

TAVR with the self-expanding ACURATE neo did not meet non-inferiority compared to the balloon-expandable SAPIEN 3 device in terms of early safety and clinical efficacy outcomes. An early composite safety and efficacy endpoint was useful in discriminating the performance of different TAVR systems.

Funding

Boston Scientific (USA).

Introduction

Transcatheter aortic valve replacement (TAVR) has been developed as an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis at increased risk for surgery. Accumulating evidence from randomised clinical trials in patients at extreme, high, intermediate, and low risk for surgery catalysed the rapid adoption of TAVR for the treatment of severe aortic stenosis in older patients across the entire risk spectrum.1, 2, 3, 4, 5, 6, 7

Available TAVR systems differ with respect to mechanism of deployment, size (in terms of vascular access), potential for repositionability, haemodynamic performance, and risk of atrioventricular conductance disturbances. Thus, although landmark clinical trials have established TAVR as the preferred treatment option in older patients with severe aortic stenosis, the generalised applicability of these findings to the entire range of available TAVR systems is challenged by the variety among these systems. Evidence from strategy trials1, 2, 3, 4, 5, 6, 7 signals the need for randomised comparisons between available transcatheter valves to identify an appropriate endpoint to critically assess device-specific performance during short-term and long-term follow-up. Only two previously published randomised controlled trials have compared TAVR devices: the CHOICE trial8 compared a first-generation balloon-expandable device to a first-generation self-expanding device with regard to device success based on the Valve Academic Research Consortium (VARC) definition; and the REPRISE III trial9 compared a mechanically expanding device to a self-expanding device with respect to a 30-day composite safety endpoint and a 1-year composite efficacy endpoint.

Research in context

Evidence before this study

Transcatheter aortic valve replacement (TAVR) with balloon-expandable valves has been associated with favourable clinical outcomes compared with surgical aortic valve replacement in patients with symptomatic severe aortic stenosis across the spectrum of risk. With the anticipated expansion of TAVR into lower-risk patients, transcatheter device-versus-device trials gain increasing relevance in view of periprocedural and long-term outcomes. We searched PubMed and conference abstracts on Aug 5, 2019, with no language restrictions, using the following search terms “transcatheter aortic valve replacement” OR “transcatheter aortic valve implantation” AND “randomized”. Our search found three head-to-head randomised comparisons, two of which compared a balloon-expandable valve with a self-expanding valve. The CHOICE trial showed superior device success in patients treated with second-generation balloon-expandable valves (Edwards SAPIEN XT) compared with first-generation self-expanding valves (CoreValve) in 241 patients with aortic stenosis at high-risk for surgery. The SOLVE-TAVI trial showed equivalence of a newer-iteration balloon-expandable device (Edwards SAPIEN 3) compared with a newer-iteration self-expanding device (Evolut R) with regard to a composite of all-cause death, stroke, moderate-to-severe aortic regurgitation, or permanent pacemaker implantation at 30 days in 447 patients with severe symptomatic aortic stenosis. The ACURATE neo system is a novel, self-expanding transcatheter heart valve that has been associated with similar clinical outcomes, lower transvalvular gradients, and lower rates of permanent pacemaker implantation compared with balloon-expandable valves in a propensity score-matched analysis of 1121 patients. Conversely, rates of paravalvular leakage were higher in patients treated with the ACURATE neo valve compared with those treated with the balloon-expandable SAPIEN 3 prosthesis. No evidence from randomised controlled trials comparing ACURATE neo with the benchmark balloon-expandable SAPIEN 3 system is available.

Added value of this study

The SCOPE I trial is the first randomised trial to compare the self-expanding ACURATE neo valve with the balloon-expandable SAPIEN 3 prosthesis in patients with severe symptomatic aortic stenosis. The study hypothesis of non-inferiority of the ACURATE neo compared with the SAPIEN 3 with regard to a primary safety and efficacy composite endpoint assessed at 30 days was not met. In a secondary analysis, the balloon-expandable SAPIEN 3 device was superior to the self-expanding ACURATE neo device with respect to the primary composite endpoint. The difference was largely driven by valve-related dysfunction due to paravalvular aortic regurgitation as assessed by an independent echocardiographic core laboratory. Most of the individual clinical components of the primary endpoint were similar between groups. The composite safety and efficacy endpoint used in this trial was able to adequately discriminate the performance of individual TAVR devices at short-term follow-up.

Implications of all the available evidence

Conceptual differences between available devices for TAVR affect safety and efficacy endpoints and challenge the generalisability of landmark strategy trials (TAVR vs surgical aortic valve replacement) to all available devices. TAVR with the ACURATE neo device is associated with higher incidence of paravalvular leakage than that of the SAPIEN 3 prosthesis, while rates of death, stroke, and myocardial infarction are similar. An early composite safety and efficacy endpoint could be useful in discriminating the performance of future iterations of TAVR systems.

Multiple versions of the balloon-expandable SAPIEN TAVR system (Edwards Lifesciences, Irvine, CA, USA) have been investigated in several randomised trials and prospective registries, and have shown excellent safety and efficacy outcomes.1, 4, 6, 10, 11 The ACURATE neo (Boston Scientific, Marlborough, MA, USA) transcatheter heart valve is a novel, self-expanding TAVR prosthesis associated with favourable outcomes in non-randomised studies.12, 13, 14, 15 The current randomised trial (SCOPE I) is the first study to compare the safety and efficacy of the ACURATE neo with the SAPIEN 3 TAVR prosthesis in patients with severe, symptomatic aortic stenosis undergoing transfemoral TAVR.

Section snippets

Study design and participants

The SCOPE I trial is an investigator-initiated, multicentre, assessor-masked, randomised controlled trial conducted at 20 tertiary, high-volume heart valve centres in Germany, the Netherlands, Switzerland, and the UK. The trial was designed to compare the safety and efficacy of two TAVR systems: the ACURATE neo bioprosthesis, which combines a self-expanding nitinol frame with three porcine pericardial leaflets, and a stent body with an outer and inner pericardial skirt;16 and the SAPIEN 3

Results

Between Feb 8, 2017, and Feb 2, 2019, up to 5132 patients were screened and 739 (14%) patients were included at 20 European sites (full screening and inclusion numbers are presented in the appendix [pp 9–10]). 372 patients were allocated to the ACURATE neo and 367 to the SAPIEN 3 TAVR system. Eight (1%) patients withdrew consent before 30-day follow-up, none of whom had an adverse event relevant to the primary endpoint up to the time of withdrawal. None of the remaining patients were lost to

Discussion

In this multicentre, randomised non-inferiority trial of older patients with symptomatic severe aortic stenosis at increased surgical risk, TAVR with the self-expanding ACURATE neo prosthesis was not non-inferior to the balloon-expandable SAPIEN 3 prosthesis with respect to a composite safety and clinical efficacy endpoint at 30 days. Secondary analyses revealed superiority of the SAPIEN 3 compared with the ACURATE neo TAVR system with respect to the primary endpoint at 30 days, with lower

Data sharing

The SCOPE I trial is an investigator-initiated trial with multiple pre-defined sub-studies. Internal investigators who actively participated in the study and who provide a methodologically sound study proposal will be granted priority access to the study data for a period of 24 months. After 24 months, data used in this Article plus relevant documentation will be made available to external investigators (those not affiliated to the trial) whose proposed use of the data has been approved by an

References (23)

  • JJ Popma et al.

    Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients

    N Engl J Med

    (2019)
  • Cited by (0)

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    Contributed equally

    Investigators are listed in the appendix

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