The introduction of transcatheter aortic valve replacement (TAVR) has over the past decade transformed the treatment of patients with severe aortic stenosis (AS). This is due, in part, to the unprecedented level of robust evidence that was generated in the pivotal regulatory trials facilitated not only the clinical adoption of TAVR but has also served to inform the clinical guideline recommendations. Through a series of trials of a balloon-expandable and a self- expanding TAVR devices studied in descending tiers of surgical risk beginning with inoperable or prohibitive risk followed sequentially by high, intermediate and low surgical risk patients, approximately 9,000 patients were randomized, the highest level of evidence generation. In all of these trials, TAVR was found to be either non-inferior (equivalent) to surgical aortic valve replacement or superior. (1-8) This has led to a “rational dispersion” of this new therapy and greatly expanded the number of patients with aortic stenosis eligible for and/or willing to undergo treatment.
It is a basic principle of clinical adoption of new therapies that when the outcomes (at least in the short and intermediate term) of two different treatments are equivalent, then the less invasive treatment, e.g.TAVR vs. SAVR or PCI vs. CABG, is preferred by the patient and their referring providers. Because of the less invasiveness, along with the high level of evidence and the simplicity of the procedure the number of TAVR procedures eclipsed the number of SAVR procedures in 2018 and in 2021, over eighty percent of all isolated aortic replacements were performed by a transcatheter approach in the US.
Professional society guideline writing committees evaluate the evidence (or lack thereof) for a particular therapy and make recommendations based on that evidence to make recommendations to help inform and guide clinicians caring for patients. This includes the level of evidence (LOE) supporting a particular class of recommendation. In the case of options for treatment of AS, the recommendations were all LOE A, the highest level based on the evidence obtained from multiple randomized trials. Since TAVR was either superior or non-inferior to SAVR at all levels of surgical risk, the guideline recommendations were based not on risk but upon patient age, < 65 years, 65-80 years and >80 years reflecting the patients studied in the clinical trials. While an appropriate criticism of the guidelines is that there is little evidence to address durability concerns beyond five years, there is also no evidence of premature structural valve deterioration in TAVR valves vis-à-vis surgical valves, hence the Class I recommendation for TAVR and 2a for SAVR in patients > 80 years, reflective of the less invasive approach and more rapid recovery in the elderly.
One concern of randomized trials is that they are performed in highly selected patients and treated by experienced experts in high volume centers and hence, the outcomes generated in this selective trial environment may not be “generalizable to the real world”. This is where the value of the recently published UK TAVI Trial helps to further inform us and supports the published guidelines. (9) This trial was a pragmatic trial which included all eligible patients aged 70 or over treated at all 34 centers performing TAVR in the UK, with varying levels of operator experience and with operator discretion to use any approved transcatheter of surgical valve. The findings at one year were that TAVR was once again non-inferior to surgery at one year, thus confirming those of the pivotal regulatory trials and expanding the knowledge base that the highly selected pivotal trial findings are indeed able to be replicated in clinical practice.
Further evidence that this is the case is supported by the findings from the STS/ACC Transcatheter Valve Therapy (TVT) Registry which tracks all TAVR procedures performed in the US. In 2021, there were >92,000 TAVR procedures performed in 790 centers. (10) The overall 30-day mortality was 2.1% with an 89% one-year survival. The 30-day mortality in high, intermediate and low risk patients was 3.5%, 1.5% and 0.8% respectively. One-year survival in low-risk patients was 95%.
Never before in the introduction of new medical devices has such a robust body of evidence been generated to inform clinicians, regulators, payers, and patients. The society guidelines, both US and European reflect this evidence. Since the guidelines have been published, newer evidence from the UK TAVI pragmatic trial and from the TVT Registry confirm that the pivotal trials and the guidelines got it right. The caveat of course is that these findings and recommendations are reflective of short and intermediate term outcomes with very little data available beyond five years. There are previous experiences in surgical valves with no apparent concerns at five years only to learn of premature structural valve deterioration at seven and eight years (Toronto SPV and Mitraflow valves). Guidelines by design must reflect the best current available evidence and if and when new evidence is generated that is at odds with current recommendations, the guidelines will be modified accordingly. Meanwhile, the newest evidence from the UK TAVI Trial and TVT Registry support adherence to the current guidelines.
- Leon MB, Smith CR, Mack M, et al; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363 (17):1597-1607. doi:10.1056/NEJMoa1008232
- Smith CR, Leon MB, Mack MJ, et al; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198. doi:10.1056/ NEJMoa1103510
- Mack MJ, Leon MB, Smith CR, et al; PARTNER 1 Trial Investigators. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015;385 (9986):2477-2484. doi:10.1016/S0140-6736(15) 60308-7
- Adams DH, Popma JJ, Reardon MJ, et al; US CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014;370(19):1790-1798. doi:10.1056/NEJMoa1400590
- Gleason TG, Reardon MJ, Popma JJ, et al; CoreValve US Pivotal High Risk Trial Clinical Investigators. 5-year outcomes of self-expanding transcatheter versus surgical aortic valve replacement in high-risk patients. J AmColl Cardiol. 2018;72(22):2687-2696. doi:10.1016/j.jacc.2018.08. 2146 Leon MB, Smith CR, Mack MJ, et al; PARTNER 2 Investigators. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374(17):1609-1620. doi:10.1056/ NEJMoa1514616
- Mack MJ, Leon MB, Thourani VH, et al; PARTNER 3 Investigators. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380(18):1695-1705. doi:10.1056/NEJMoa1814052
- Popma JJ, Deeb GM, Yakubov SJ, 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;380 (18):1706-1715. doi:10.1056/NEJMoa1816885
- The UK TAVI Trial Investigators. Effect of transcatheter aortic valve implantation vs surgical aortic valve replacement on all-cause mortality in patients with aortic stenosis: a randomized clinical trial. JAMA. Published May 17, 2022. doi:10.1001/ jama.2022.5776
- STS/ACC TVT Registry. Presented at the TVT Registry Stakeholders Advisory Group, April 1, 2022, Washington, DC
Trial Co-PI Partner Trial of Edwards Lifesciences
Member of the Writing Committee of the 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease
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