Game Changer: Success Positions TAVR for Expanded Indications

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SAPIEN 3 has a smaller delivery system and design than the first-generation iteration of the valve.
Source: Edwards Lifesciences

The prevalence of degenerative aortic stenosis in the growing elderly population has contributed to the demand for innovative and less invasive new technology for aortic valve replacement. Though surgical results are traditionally excellent, many patients are not offered surgical aortic valve replacement (SAVR) due to high surgical risk or inoperability despite the fact that untreated aortic stenosis carries a mortality of up to 50 percent at five years (Lancet 2009;373:956-966). The transcatheter approach has been proven to be an effective aortic valve replacement option for patients with aortic stenosis who are either very high risk or not candidates for surgical therapy. As transcatheter valve technology evolves with improved delivery systems, valve design and patient selection, the likelihood of indications being expanded to include intermediate- and even low-risk patients is likely.

The early proving ground for TAVR in the United States began with the PARTNER (Placement of AoRtic TraNscathetER Valves) I Trial, which used the first-generation SAPIEN balloon expandable valve (Edwards Lifesciences). This study showed both improved mortality in inoperable patients who received TAVR compared with medical therapy, as well as comparable one-year survival, reduction in symptoms and improved valve hemodynamics between high-risk SAVR and TAVR. It should be noted, however, that TAVR patients had higher rates of post-implant paravalvular leak, stroke and major vascular complications (N Engl J Med 2010;363:1597-1607; N Engl J Med 2012;366:1686-1695). In 2011, the first-generation SAPIEN valve became the first TAVR valve to be approved by the FDA for inoperable patients; in 2012, it was approved for high-risk patients.

The second important clinical trial to evaluate TAVR was the Core Valve Pivotal trial (Medtronic), which randomized high-risk patients with aortic stenosis to conventional surgery vs. TAVR. The TAVR patients had lower mortality from any cause at one year compared to the surgical group (N Engl J Med 2014;370:1790-1798). The self-expanding CoreValve received FDA approval in 2014. Newer generations of both the SAPIEN 3 (Edwards Lifesciences) and the Evolut R (Medtronic) valves have been developed with smaller delivery systems and valve design, including skirts to minimize paravalvular leaks. The early results of studies comparing these TAVR valves with SAVR in intermediate-risk patients have been promising. At 30 days, mortality was 1.1 percent in intermediate-risk patients treated with SAPIEN 3 (American College of Cardiology 2015 Scientific Sessions).

Numerous other TAVR valves are in clinical trials and eventually will compete for a share of what is already an important and lucrative market, estimated to be $5 billion by 2020. To monitor the use of this new technology in the United States, The Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC), in collaboration with the FDA and the Centers for Medicare & Medicaid Services, developed the STS/ACC Transcatheter Valve Therapy (TVT) Registry. As of December 2015, 411 sites were performing TAVR in the United States, and approximately 40,000 procedures had been entered into the TVT Registry. Depending on the results of the intermediate-risk studies, the demand for TAVR will continue to increase as the number of valve centers grows and indications are expanded.

In addition to clinical advantages, the economics of TAVR vs. SAVR are an issue. There is a significant difference between the costs of the valves themselves: approximately $5,000 for SAVR and $30,000 for TAVR. Sophisticated analyses of the PARTNER trial used quality-adjusted life years (QALYs), a composite of the extra years of life gained factored with the quality of life, to determine the cost effectiveness of TAVR (Int J Technol Assess Health Care 1989;5[4]:559-575). The trial showed that the 12-month costs and QALYs were similar for TAVR and SAVR in the overall study population with a slight advantage for TAVR performed via the transfemoral artery (N Engl J Med 2014;370:1790-1798). These advantages have the potential to become more apparent should the indications for TAVR be extended to intermediate- and subsequently lower-risk groups, although TAVR currently has a significant negative contribution margin. Potential opportunities for cost savings include decreased use of general anesthesia, decreased intensive care unit utilization and significantly decreased hospital lengths of