The ACURATE investigational device exemption (IDE) trial results indicate that the Acurate neo2 TAVI valve (Boston Scientific) did not achieve noninferiority compared to existing devices in patients with symptomatic severe aortic stenosis across all operative risk levels. The trial, presented at TCT 2024, raises questions about the valve's potential approval in the United States, despite its availability in Europe and other regions.
Primary Endpoint Missed
At 1 year, the composite rate of all-cause mortality, stroke, or rehospitalization was 16.16% in patients receiving the Acurate neo2, compared to 9.53% in those treated with Evolut (Medtronic) or Sapien (Edwards Lifesciences) valves. According to Michael Reardon, MD (Houston Methodist DeBakey Heart & Vascular Center, TX), this difference failed to meet the pre-specified noninferiority margin of 8%.
Potential Factors Influencing Results
Reardon suggested several factors that may have contributed to the trial's outcome, including the COVID-19 pandemic's impact on enrollment, staffing, supply chain disruptions, and operator experience. The infrequent use of the Acurate neo2 at trial sites, with 72% of operators performing five or fewer cases during the study, potentially led to unfamiliarity with the device.
Underexpansion Concerns
A post-hoc review identified underexpansion of the valve frame in approximately 20% of Acurate neo2 implants. Reardon noted that valve underexpansion is increasingly recognized as a significant issue affecting long-term valve outcomes. Analyses focusing on well-expanded valves showed more similar outcomes between the trial arms.
Trial Design and Patient Population
The ACURATE IDE trial enrolled 1,500 patients (mean age 79 years, 52% women) with symptomatic severe aortic stenosis across all operative risk levels at 70 centers in the US and Canada. Patients were randomized to receive either the Acurate neo2 or commercially available balloon-expandable Sapien valves (Sapien 3 and Sapien 3 Ultra) or self-expanding Evolut valves (CoreValve Evolut R, Evolut PRO, Evolut PRO+, Evolut FX). The mean STS score was approximately 2.8%, with 27% of patients at high/extreme risk, 38% at intermediate risk, and 35% at low risk.
Procedural Differences
Procedural characteristics were generally similar between the Acurate neo2 and control arms. However, the Acurate neo2 arm had more frequent predilation (99.6% vs 33.0%) and postdilation balloon use (26.1% vs 11.3%; P < 0.001 for both). Predilation, using a balloon 1-mm smaller than the annular diameter, was required for the Acurate neo2.
Clinical Outcomes
Kaplan-Meier analysis revealed a significantly higher 1-year rate of the primary endpoint in the Acurate neo2 arm (5.8% higher; 95% CI 2.4%-9.1%). While each component of the primary endpoint was numerically higher in the Acurate neo2 arm, only the difference in stroke rates reached statistical significance. Patients treated with Acurate neo2 also had higher rates of CV death (3.7% vs 1.8%) and MI (2.4% vs 0.7%).
Echocardiographic Findings
Echocardiographic outcomes showed that Acurate neo2 provided mean gradients similar to Evolut valves and lower than Sapien valves, with Doppler velocity index values comparable to self-expanding valves. At discharge, none/trace paravalvular regurgitation (PVR) was present in 75.9% of Acurate neo2-treated patients, 71.2% of Evolut valve recipients, and 93.3% of Sapien valve recipients.
Addressing Underexpansion
Investigators identified that underexpanded valves had higher-velocity, turbulent flow, reduced washout, and leaflet kinking. Post-hoc analyses indicated that underexpanded valves had higher 1-year rates of death, stroke, or hospitalization (18.8% vs 12.4%; P = 0.050), death (7.4% vs 3.7%; P = 0.054), and stroke (11.0% vs 3.5%; P < 0.001). Reardon suggested that addressing underexpansion through proper imaging and balloon dilation could improve outcomes.
Valve Attributes and Future Prospects
Despite the trial's outcome, Reardon emphasized the Acurate neo2's unique attributes, including its top-down deployment, which stabilizes the valve and allows for accurate deployment of a short-frame, self-expanding valve. This design offers rapid, reliable deployment, coronary access, and a low pacemaker rate, combined with the superior hemodynamics of a self-expanding valve and commissural alignment. Jan-Malte Sinning, MD (Cellitinnen-Krankenhaus St. Vinzenz, Cologne, Germany), noted that the Acurate neo2 combines features of self-expanding valves with improved coronary artery access but may perform worse in heavily calcified annuli. Poonam Velagapudi, MD (University of Nebraska Medical Center, Omaha), suggested that the currently available valves have a very high standard, and it is difficult to displace them.
