SCOPE II: New self-expanding bioprosthetic valve fails to demo noninferiority to existing option

The novel self-expanding bioprosthetic ACURATE neo valve did not demonstrate noninferiority to the currently available CoreValve Evolute valve in patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), according to the SCOPE* II trial.

“[Transfemoral] TAVR with the ACURATE neo valve did not meet noninferiority compared with the CoreValve Evolut bioprosthesis with respect to a composite of death or stroke at 1 year,” presented Professor Corrado Tamburino from the University of Catania, Catania, Italy, at TCT Connect 2020.

In this multinational trial (23 European sites), 796 patients aged ≥75 years (mean age 83.2 years, 68 percent female, mean STS-PROM** score 4.6 percent) with symptomatic severe aortic stenosis scheduled to undergo TAVR were randomized 1:1 to receive either the ACURATE neo or CoreValve Evolute valve. Patients mostly had New York Heart Association class III or IV (66 and 63 percent, respectively).

At 1 year, all-cause mortality or stroke occurred in 15.8 and 13.9 percent of ACURATE neo and CoreValve Evolute recipients, respectively, in the intention-to-treat (ITT) population (absolute risk difference, 1.8 percent, upper 1-sided 95 percent confidence interval [CI] limit 6.1 percent [noninferiority margin 6 percent]; p_{noninferiority}=0.0549). In the per-protocol*** population, the rates were 15.3 and 14.3 percent, respectively (absolute risk difference, 1.0 percent, upper 1-sided 95 percent CI limit 5.4 percent; p_{noninferiority}=0.0314). [TCT Connect 2020, Late-Breaking Clinical Trial Session II; Circulation 2020;doi:10.1161/CIRCULATIONAHA.120.051547]

“Because the results of the ITT and per-protocol analyses were inconsistent, noninferiority of the ACURATE neo was not established for the primary endpoint,” said Tamburino.

Implantation of a new permanent pacemaker was less likely with the ACURATE neo valve than the CoreValve Evolut valve at 30 days (10.5 percent vs 18.0 percent; absolute risk difference, -7.5 percent; p_superiority=0.0027). 

Secondary analysis suggested an increased risk of cardiac death at 1 year with the ACURATE neo vs CoreValve Evolute valve (8 percent vs 4 percent; risk difference, 4.5 percent; p=0.01), though this had limited statistical power. There was an increased risk of new left bundle branch block with the CoreValve Evolute vs ACURATE neo valve in the ITT (19 percent vs 14 percent; risk difference, -5.2 percent; p=0.048), but not the per-protocol population. Risk of other outcomes such as stroke, myocardial infarction, life-threatening or major bleeding, or tachyarrhythmia leading to haemodynamic instability or warranting treatment was comparable between groups.

Moderate-to-severe aortic regurgitation was more common with the ACURATE neo than the CoreValve Evolute valve at 30 days (9.6 percent vs 2.9 percent) and 1 year (4.0 percent vs 3.3 percent; p<0.0001 at both time points).

The researchers acknowledged that 1-year follow-up may have been insufficient to identify long-term differences in outcomes. Furthermore, the trial was not powered to detect differences in individual clinical endpoints except for new permanent pacemaker implantation.

“TAVR is expanding worldwide as a treatment option for patients with symptomatic severe aortic stenosis. Head-to-head comparisons of commercially available valves are important to fully appreciate their strengths and limitations, and meaningfully inform the operators at the time of valve selection,” they said.

The researchers also noted that the ACURATE neo valve used in the trial was the first iteration of the valve and was compared with the current iteration of the CoreValve Evolute valve.

“Design improvements are necessary to mitigate the risk of paravalvular regurgitation with the ACURATE neo valve and improve clinical outcomes at the early and mid-term,” they said.