Randomized Trial Shows That Transcatheter Aortic-valve Replacement is Non-inferior to Surgery in Low Risk Patients

A study by Dr. Jeffrey Popma and colleagues published in the New England Journal of Medicine showed that transcatheter aortic-valve replacement (TAVR) was non-inferior to surgery with respect to death or the occurrence of a disabling stroke by 24 months in the low-risk group of patients with aortic stenosis. Previous studies showed that in patients with severe aortic stenosis who were at high risk of complications or death from surgery, TAVR with a self-expanding supra-annular bioprosthesis had better outcomes than medical therapy or surgery. However, there was not enough evidence to advocate the use of TAVR instead of surgery in a younger, healthier population. The authors aimed to address this knowledge gap through this study.

In this multinational, randomized, non-inferiority clinical trial, patients with severe aortic stenosis who had a less than 3% risk of death by 30 days with surgery were randomized to either TAVR or surgery. Aortic valve stenosis was defined as an aortic valve-area of 1.0 cm² or less or a mean gradient of 40 mm Hg or maximal aortic-valve velocity of 4.0m or more per second when measured at rest. Patients randomized to TAVR received one of three self-expanding supra-annular bioprostheses (CoreValve, Evolut R or Evolut PRO). In the surgery arm, the size and type of surgical valve were at the discretion of the surgeon, but patients who were to receive a mechanical valve were excluded. The primary endpoint was a composite of death from any cause or disabling stroke at 24 months. A secondary 30-day composite secondary safety endpoint was also assessed and consisted of death, disabling stroke, life-threatening bleeding, major vascular complications or type 2 or 3 acute kidney injury.

Of the 1,468 patients who were randomized, 1,403 patients underwent the procedure they were randomized to (725 in the TAVR group and 678 in the surgery group). The incidence of death or disabling stroke (the primary outcome) was 5.3% in the TAVR group and 6.7% in the surgery group. While the criteria for noninferiority was met, the criteria for superiority was not. The 30-day composite secondary safety endpoint occurred in 5.3% of patients in the TAVR group and 10.7% of patients in the surgery group. The TAVR group had a lower incidence of disabling stroke (0.5% vs 1.7%), bleeding complications (2.4% vs 7.5%), acute kidney injury (0.9% vs 2.8%) and atrial fibrillation (7.7% vs 35.4%) but a higher incidence of permanent pacemaker use (17.4% vs 6.1%) and moderate or severe aortic regurgitation (17.4% vs 6.1%). At 12 months, patients in the TAVR group had a lower aortic valve gradient (8.6 mm Hg vs 11.2 mm Hg). Additionally, while both groups had an improvement in their function and quality of life by 12 months (assessed using the Kansas City Cardiomyopathy Questionnaire), patients in the TAVR group had a better recovery at 30 days.

It is important to note that the study has its limitations. Not all patients had 24 months of follow up. In fact, this prespecified analysis was performed when the 850^th patient reached 12 months of follow up. “Definitive conclusions regarding the advantages and disadvantages of TAVR as compared with surgery await long-term clinical and echocardiographic follow-up, which is planned to continue through 10 years for all patients,” Dr. Popma noted.  Dr. Howard Herrmann wrote, “Although some cardiologists and surgeons may be concerned about uncertainties with TAVR’s long-term durability, other studies’ 5- to 8-year follow-up data look promising.” When talking about the future of TAVR, Dr. Hermann also said, “TAVR will likely be quickly approved as an alternative for low-risk patients who will prefer the less-invasive approach. Physicians will need a reason to refer for surgery, and hospitals will be forced to confront the lower profitability of the TAVR procedure as it replaces surgery for even more patients.” Of note, another study published in the New England Journal of Medicine by Dr. Michael Mack showed that in patients with severe aortic stenosis who were at low surgical risk, the rates of death, stroke or rehospitalization by 1 year was lower in the TAVR group. There is still a concern regarding long term outcomes of TAVR but this will be addressed in the future, once the follow-up data is published.