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Study Summary

PARTNER 3: Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients

A total of 71 centers recruited and subsequently randomized 1000 patients with symptomatic high-grade aortic stenosis and an STS PROM <4% to undergo either transfemoral transcatheter aortic-valve replacement (TAVR) with a balloon-expandable SAPIEN 3 valve or surgical aortic valve replacement (SAVR) with a bioprosthetic valve. Mean age and STS PROM were 73 years and 1.9%, respectively. The composite of death from any cause, stroke, or rehospitalization at 12 months occurred in 42 patients (8.5%) in the TAVR group and 68 patients (15.1%) in the surgical group (see accompanying Hurst's Central Illustration). The absolute difference of 6.6% met the pre-specified requirements for non-inferiority and superiority of TAVR. Additionally, at 30 days, TAVR patients experienced lower rates of stroke (0.6% vs. 2.4%, = 0.02), death or stroke (1.0% vs. 3.3%, = 0.01), new-onset atrial fibrillation (5.0% vs. 39.5%, <0.001), and death or low Kansas City Cardiomyopathy score (3.9 vs. 30.6, <0.001), as well as shorter duration of index hospitalization (3 days for TAVR vs. 7 days for SAVR, <0.001). There was no significant difference between groups regarding major vascular complications, new permanent pacemaker insertion (6.5% for TAVR vs. 4.0% for SAVR), or moderate or greater paravalvular regurgitation.

Evolut Low Risk: Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients

In this case, a total of 1468 patients with symptomatic high-grade aortic stenosis and an STS PROM <3% were randomized to transfemoral TAVR with a self-expanding supra-annular bioprosthesis or SAVR with a bioprosthetic valve. Mean age and STS PROM were 74 years and 1.9%, respectively. At 24 months, the incidence of the primary end point, a composite of death or disabling stoke, occurred in 5.3% of the TAVR group and 6.7% of the surgical group (see accompanying Hurst's Central Illustration). These results met the pre-specified criteria for non-inferiority of TAVR (P <0.05 for noninferiority, P >0.05 for superiority). The incidence of death from any cause at 2 years was 4.5% in both groups, and the rate of disabling stroke was 1.1% and 3.5% in the TAVR and SAVR groups, respectively. At 30 days, the TAVR group had a lower incidence of disabling stroke, bleeding complications, acute kidney injury, and atrial fibrillation. At the same time point, however, the TAVR group did have higher incidences of moderate/severe aortic regurgitation (3.5% vs. 0.5%) and permanent pacemaker implantation (17.4% vs. 6.1%).

Commentary

Study Strengths: Both of these studies were randomized, controlled trials with sufficient enrollment to meet pre-specified goals. Their results are comparable for a similar cohort of patients based on age, comorbidities, and surgical risk and therefore complement each other.

Study Limitations: The major limitation for both studies is their brief duration of follow-up (12 and 24 months for PARTNER 3 and Evolut Low-Risk, respectively). This timeline is not sufficient to understand the significance of structural valve degeneration in a low-risk cohort of patients receiving TAVR. These data also cannot be extrapolated to all low-risk patients, especially patients with bicuspid aortic valves or who have concerns regarding taking antithrombotic medications, as they were excluded. Finally, as in prior TAVR trials, end points were not adjudicated in a blinded fashion and cannot be extrapolated to centers with less procedural experience implanting TAVR valves.

The PARTNER 3 trial, while showing both non-inferiority and superiority of TAVR to surgery, included hospitalizations in its primary outcome. This inclusion may explain the improved outcomes compared to the Evolut Low Risk study, which included only death and disabling stroke in the 2-year primary outcome.

While the Evolut Low Risk study reports 24-month outcomes, the analysis began when 850 patients reached the 12-month cutoff, and not all data were completed for a full 24-month analysis. Additionally, only 22.3% of the Evolut Low Risk TAVR patients received the latest generation bioprosthesis and, therefore, this may not reflect the most current technology.

Next Steps/Clinical Perspective: The major goal for the future will be to continue to assess patient outcomes over a longer duration, as valve degeneration or other variables may shift the benefit away from TAVR in this group with a preserved left ventricular function and longer life expectancy. While there was a non-significant trend toward increased permanent pacemaker insertion for the Sapien valve, it would be important to assess whether the significant increase in pacemaker requirement for the Evolut valve is affected by the newer generation valves now available.

Trial References

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Mack  MJ, Leon  MB, Thourani  VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. doi: 10.1056/NEJMoa1814052
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Popma  JJ, Deeb  GM, Yakubov  SJ, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. doi: 1 0.1056/NEJMoa1816885

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