SCOPE I: A randomized trial of the ACURATE Neo vs. the SAPIEN 3 bioprosthesis in patients with severe aortic stenosis - TCT 2019

Reported from the TCT Congress 2019 in San Francisco - USA

The results of the SCOPE I trial were presented at TCT 2019 in San Francisco by Jonas Lanz, Bern University Hospital. Read the analysis by Fabien Praz.

The Methodology

Transfemoral TAVI has become an indispensable treatment modality for patients with symptomatic severe aortic stenosis across all risk categories and several TAVI systems have been approved for this purpose. Whether the implantation of different valves leads to different clinical outcomes has not been widely investigated yet.

SCOPE I is an investigator-initiated randomized clinical trial designed to compare early safety and efficacy of the self-expanding ACURATE neo to the balloon-expandable SAPIEN 3 transcatheter heart valve system in patients with symptomatic severe aortic stenosis undergoing transfemoral TAVR. The primary study hypothesis was the non-inferiority of the self-expanding ACURATE neo valve compared to the SAPIEN 3 valve. Echocardiographic data were assessed by an independent core lab.

The included patients were 75 years of age or older and had symptomatic (NYHA≥II or angina) severe aortic stenosis (aortic valve area <1cm²) and a left ventricular function of 20% or more. All were considered inoperable or at increased risk for SAVR based on risk scores and/or Heart Team recommendation. Aortic annulus dimensions and peripheral access had to be suitable for either device. The primary endpoint was a composite safety and efficacy endpoint based on the VARC-2 criteria including all-cause death, any stroke, life-threatening or disabling bleeding, major vascular complications, coronary artery obstruction requiring intervention, acute kidney injury stage 2 or higher, valve-related dysfunction requiring repeat procedure, rehospitalization for valve-related symptoms or congestive heart failure, moderate or severe prosthetic valve regurgitation or prosthetic valve stenosis at 30 days.

What were the results?

A total of 739 patients (mean age 83 years) with symptomatic severe aortic stenosis were randomized at 20 European sites – 372 were allocated to ACURATE neo and 367 to SAPIEN 3. Overall follow-up for clinical endpoints was 99% and 98% for echocardiographic core lab assessment.

At 30 days, the primary composite endpoint occurred in 23.7% of patients treated with the ACURATE Neo and 16.5% in the SAPIEN 3 group. Thus, non-inferiority of the ACURATE Neo system 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. These results were driven by a higher rate of acute kidney injury (3% versus 1%; p=0.034) and moderate or severe paravalvular aortic regurgitation (9% versus 3%) among patients treated with the ACURATE Neo bioprosthesis. Notwithstanding, the incidence of all-cause death (2% for ACURATE neo vs 1% for SAPIEN 3; p=0.09) and stroke (seven 2% versus 3%; p=0.33) did not differ between groups.

A closer look into procedural characteristics shows additional important differences between both TAVI platforms. Procedural time and contrast medium administration were significantly higher during ACURATE neo implantation, as well as the rates of pre- (88% versus 23%; p<0.0001) and postdilatation (52% versus 13%; p<0.0001). Interestingly, multiple valve implantation was more frequently needed in the ACURATE neo group (3% versus 1% in SAPIEN 3 arm; p=0.0119), while the proportion of patients requiring new permanent pacemaker implantation did not differ between arms (10% for ACURATE neo and 9% for SAPIEN 3; p=0.76).

Except for the already mentioned higher rate of moderate or severe paravalvular regurgitation, other echocardiographic parameters were favorable for the ACURATE neo bioprosthesis with a higher aortic valve area (median 1.73cm² versus 1.47cm² for the SAPIEN 3 valve; p<0.0001) and a lower mean transaortic gradient (median 7 versus 11mmHg; p<0.0001).

My take on this study

In summary, the ACURATE neo TAVI system did not meet the prespecified criteria of non-inferiority compared to the SAPIEN 3 valve in this large randomized study at 30 days. In a secondary analysis, superiority of the SAPIEN 3 platform was established because of a lower rate of moderate or severe paravalvular regurgitation and acute kidney injury stage 2 or 3. As an important message for future comparative device studies in the TAVI field, the use of a composite safety and efficacy endpoint enabled the detection of significant differences between arms already after 30 days of follow-up.

Owing to its supra-annular design, hemodynamic findings (valve area and mean transvalvular gradient) were in favour of the ACURATE neo valve, while pacemaker rate was low in both arms. Of note, the ACURATE neo system used in SCOPE I is a first-generation device and future iterations will specifically address some of the issues raised in the study, especially through the implementation of a skirt intended to improve annular sealing. A second similar study, SCOPE II, will compare the ACURATE neo to the EVOLUT R system with respect to a composite of all-cause death and stroke at 1 year.

SCOPE I is one of the first and largest randomized studies comparing TAVI devices and provides meaningful information concerning device safety and performance that can be used for valve selection, paving the path for individually tailored therapeutic solutions.