Transcatheter vs surgical aortic valve replacement in aortic stenosis patients at low surgical risk: 3-year outcomes from the Evolut Low Risk trial
Reported from ACC.23/WCC
Luigi Biasco provides his take on the clinical trial presented by John K. Forrest from Yale University School of Medicine, New Haven, Connecticut, USA during the 2023 ACC/WCC annual congress held in New Orleans, Louisiana.
Why this study? – the rationale/objective
This study reports on the 3-year results of the Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients Trial.
While TAVR has become the treatment of choice in patients with severe aortic stenosis who are at intermediate and high surgical risk, few data are currently available on outcomes in patients at low surgical risk.
In fact, randomized data of TAVR vs surgery in intermediate and high-risk patients demonstrated similar survival outcomes at 5 years.
Short-term data in low-risk patients have shown comparable outcomes between TAVR and SAVR up to two years, nonetheless, longer-term data are needed in order to guide the decision-making process.
This study aimed to compare outcomes of low surgical risk (defined as risk of death within 30 days of the procedure below 3% according to the STS score) randomized to TAVR or SAVR with the primary endpoint set as the incidence of mortality and disabling stroke.
Previous reports published in 20191 and 20222 provided as a first the Bayesian estimated incidence at 24 months then the observed 2-year rate of the primary endpoint that confirmed TAVR non-inferiority to surgery for all-cause mortality or disabling stroke.
Observed event rates resulted slightly better than those predicted by using the Bayesian analysis (2-year endpoint 4.3% in the TAVR group and 6.3% in the surgery group, p=0.084; Bayesian rates of 5.3% with TAVR and 6.7% with surgery).
The study presented during the late-breaking clinical trial session at ACC 2023 and simultaneously published in JACC3 extends the follow-up up to three years.
How was it executed? - the methodology
Patients with severe aortic valve stenosis with anatomy suitable for both TAVR and SAVR were randomized 1:1 to undergo either percutaneous aortic valve replacement with the self-expanding supra-annular valve (CoreValve, Evolut R, or Evolut PRO valve; Medtronic) or SAVR with a biological prosthesis among 86 international centres in 7 countries from March 2016 to May 2019.
Patients with bicuspid aortic valve or with other anatomical characteristics that might have hampered TAVR results such as bulky annular calcifications have been excluded from the study.
The trial aimed at assessing both clinical outcomes and valve performance at a mid-term follow-up. Outcomes were assessed in patients who underwent an attempted implant (“as-treated” cohort).
Primary endpoint was defined as the composite of death or disabling stroke at 3 years while the composite of death from any cause, disabling stroke, heart failure rehospitalization or aortic valve-related rehospitalization was set as the secondary endpoint.
In addition, quality of life (assessed with Kansas City Cardiomyopathy Questionnaire overall summary score) functional capacity, incidence of prosthesis–patient mismatch, clinical and subclinical valve thrombosis were also evaluated.
Major findings
1,414 patients were enrolled in the study, 730 underwent attempted TAVR (mean age 74.1 y, mean STS score 2.0%, 35% women, majority of patients received the Evolut R platform) and 684 underwent attempted SAVR (mean age 73.7 y, mean STS score 1.9%).
Three-year follow-up was complete in 96.4% in TAVR and 91.2% in SAVR.
The composite primary endpoint of all-cause mortality or disabling stroke occurred in 7.4% of patients randomized to TAVR as compared to 10.4% in surgical patients (HR 0.70; 95% CI 0.49-1.00, p=0.051). Most of the events occurred early after the procedure leading to an early separation of time to event curves, maintained over time up to three years.
When considering the components of the primary endpoint, both all-cause mortality and disabling stroke were numerically favourable towards TAVR (all-cause mortality TAVR 6.3% vs SAVR 8.3%, p=0.16; disabling stroke TAVR 2.3% vs 3.4% in SAVR, p=0.19).
The rate of secondary composite endpoint was lower, borderline statistically significant, in TAVR (TAVR 13.2 % vs SAVR 16.8%, p=0.050).
PM implant rate was higher in TAVR (23.2% vs 9.1%, p>0.001) while new-onset AF was most commonly observed after SAVR (40.0% vs 13.1%, p<0.001).
No differences in the incidence of clinical and subclinical valve thrombosis among treatment arms were observed with rates well below 1%.
Valve performance at 3 years was also evaluated with the vast majority of patients in both arms showing no or trace PVL (TAVR 78.7% vs SAVR 97.3%). TAVR patients showed mild PVR in 21.3% of cases, nonetheless, this finding was not associated with a signal indicating potential clinical harm.
Data on transcatheter valve hemodynamics were also reassuring showing a stable mean gradient of about 9 mmHg throughout the entire follow-up.
Interestingly, incidence of moderate or severe prosthesis-patient mismatch (VARC-3 defined) was higher among surgical patients (SAVR 25.1% vs TAVR 10.6%, p<0.001). Valve reinterventions rate at 3 years was low in both groups (TAVR 1.0% vs SAVR 0.9%, p=0.92).
Finally, no differences in quality-of-life measures according to the KCCQ score were evident at three years with patients in both treatment arms showing a consistent improvement in QoL.
Critical reading
The results of the Evolut Low Risk trial confirm previous evidence obtained in high and intermediate-risk patients showing that transcatheter aortic valve replacement compares favourably to surgery and expands those findings to a younger population of patients at low surgical risk.
Notably, good short-term outcomes previously reported in this cohort of patients were confirmed at a longer follow-up showing that the acute benefit provided by TAVR is maintained over time, an evidence of relevant clinical interest.
Clearly, while the results of this trial are encouraging, several considerations have to be taken into account prior to expanding TAVR treatment outside the indications of current ESC guidelines that suggest referring to TAVR older (≥75 years), high-risk (STS-PROM/ EuroSCOREII>8%) patients or those unsuitable for surgery.
Mean age of patients enrolled in the trial was 74 years, thus with an estimated life expectancy significantly longer than the 3-year follow-up currently available.
From a clinical perspective, this class of younger patients at low surgical risk has a low rate of associated comorbidities such as congestive heart, failure, coronary artery disease, diabetes, end-stage renal disease or COPD, thus with no competitive causes of death that might impact on short or mid-term outcomes emphasizing the need for optimal acute outcomes maintained over time.
Clearly, long-term valve durability, capability of easy coronary re-access and strategies to tackle failing prostheses, represents the crucial points that, whether solved, will definitely open the doors of TAVR to a younger, lower-risk population.
References:
- Popma JJ, et al. Evolut Low Risk Trial Investigators. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1706-1715. doi: 10.1056/NEJMoa1816885. Epub 2019 Mar 16. PMID: 30883053.
- Forrest JK, et al. 2-Year Outcomes After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients. J Am Coll Cardiol. 2022 Mar 8;79(9):882-896. doi: 10.1016/j.jacc.2021.11.062. PMID: 35241222.
- Forrest JK et al. Three-Year Outcomes after Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients with Aortic Stenosis. Journal of the American College of Cardiology,2023, in press. https://doi.org/10.1016/j.jacc.2023.02.017.
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