Two-Year EVOLUT Data Support TAVR in Low-Risk Patients
March 16, 2019—At the American College of Cardiology's (ACC) 68th Annual Scientific Session, being held March 16–18 in New Orleans, Louisiana, the 24-month findings from the EVOLUT Low-Risk trial will be presented on March 17 by senior investigator Michael J. Reardon, MD. The trial is comparing self-expanding transcatheter aortic valve replacement (TAVR) to surgical aortic valve replacement (SAVR) in patients at low surgical risk. The study, which was funded by Medtronic, used three of the company's devices (CoreValve, Evolut R, Evolut Pro) in the TAVR arm.
The findings have been published online ahead of print by Jeffrey J. Popma, MD, et al in The New England Journal of Medicine.
According to the ACC announcement, the trial demonstrated no difference in the combined rate of disabling stroke or death from any cause at 2 years in patients treated with TAVR versus SAVR (5.3% vs 6.7%). The investigators noted that these results echo the findings in an earlier trial of intermediate-risk patients. Consequently, TAVR—which is currently approved by the FDA for the treatment of severe aortic valve stenosis in patients at intermediate and high risk for death and complications associated with surgery—appears to be a reasonable option in low-risk patients.
In the ACC announcement, Dr. Reardon commented, “We now have a minimally invasive procedure that is as good as or better than surgery, while at the same time allowing most patients to be out of the hospital within a few days and be back to their normal activities within a week, and that’s pretty important.” Dr. Reardon is Professor and Allison Family Distinguished Chair of Cardiovascular Research at Houston Methodist Hospital in Houston, Texas.
As summarized by ACC, this randomized, prospective study included 1,468 low surgical-risk patients with severe, symptomatic aortic stenosis from 86 centers in Australia, Canada, France, Japan, the Netherlands, New Zealand, and the United States. Low risk was defined as a predicted 30-day mortality of 3% or less for 30 days postsurgery and was based on a combination of clinical judgment from the local heart team and an independent screening committee.
The TAVR and SAVR arms were composed of 725 patients and 678 patients, respectively. The TAVR arm of the trial started with first- and second-generation valves (3.6%, CoreValve; 74.1%, Evolut R). The new third-generation Evolut Pro valve was introduced late in the trial and was implanted in 22.3% of patients enrolled in the TAVR arm.
The arms were well-matched in baseline characteristics such as hypertension, coronary disease, and lung disease. The study population was two-thirds men and one-third women. The earlier intermediate- and high-risk trials included a 50/50 enrollment of men and women. Dr. Reardon stated in the ACC press release that this might be because women tend to be smaller, require smaller surgical valves at surgery, and are deemed at higher surgical risk.
At 30 days, TAVR was statistically superior to SAVR in terms of the combined rate of all-cause mortality or disabling stroke (0.8% vs 2.6%). The rate of death at 1 month was not statistically different but was lower for TAVR versus SAVR (0.3% vs 1.3%), which is clinically meaningful, noted Dr. Reardon.
TAVR patients also had significantly better quality of life and hemodynamics at 30 days and shorter average length of hospital stays (2.6 days vs 6.2 days).
Dr. Reardon commented, “TAVR beat surgery at 30 days for mortality or disabling stroke, quality of life, and time in the hospital. In other words, you’re more likely to be alive without a disabling stroke, get out of the hospital sooner—in half the time—and have a better quality of life 1 month after getting a new valve.” He continued, “The mean age of patients in this study was 74, so while this is still not a young group of patients, many of them are very active and whether it be in their professional or social lives, getting back to full range of daily activities is very important to them.”
At 12 months, TAVR was still superior to SAVR for major stroke (0.8% and 2.4%), all-cause mortality (2.4% vs 3%; not statistically significant), and hospitalization for heart failure (3.2% vs 6.5%). Dr. Reardon stated, “At 1 year, patients with TAVR were more likely than surgery patients to be alive, without a disabling stroke and without a hospital admission for heart failure.”
The investigator conducted quality of life assessments using the Kansas City Cardiomyopathy Questionnaire (KCCQ) for patients to report their functional ability and wellness at baseline, 1 and 6 months, and yearly thereafter. For the KCCQ, a five-point increase is considered a small improvement in quality of life, 10 points is moderate, and 20 points is large.
Patients receiving TAVR reported significantly better quality of life, 20 points versus 9.1 points at 1 month postprocedure. By 1 year, TAVR and SAVR had similar improvements in quality of life, 22.2 points and 20.9 points, respectively.
Additionally, Dr. Reardon reported that an analysis of echocardiograms indicated that the TAVR valve worked better than the surgical valve, with better orifice (2.2 cm2 vs 2.0 cm2) and lower mean gradients at all time points in the trial.
Similar to earlier studies, TAVR had more pacemakers and more moderate to severe paravalvular leak. The TAVR group also had major vascular injury (dissection, cardiac perforation, or access-site injury). The SAVR arm had more cases of atrial fibrillation, transfusions, and acute kidney injury.
Dr. Reardon stated. “We’ve now looked at a broad risk spectrum of patients—those at high, intermediate and low surgical risk—and these series of trials have shown that TAVR is better than or as good as surgery in terms of disabling strokes and deaths from all causes. When we look at secondary outcomes of quality of life and functional recovery, these seem to favor TAVR at this point. Given this data, it now seems reasonable to consider moving TAVR in low-risk patients to a class I guideline indication on par with surgery for patients with severe aortic stenosis.”
The ACC announcement advised that a key study limitation is the relatively short follow up time. The study excluded patients with bicuspid aortic valves, with anatomic incompatibility for TAVR valves, or who need other major cardiac surgical procedures such as mitral valve repair.
Dr. Reardon noted that the investigators plan to follow patients for 10 years, which should yield important long-term data about the TAVR procedure compared with SAVR, as well as the valves. A cost-effectiveness analysis will also be conducted.