Bottom view into the Medtronic CoreValve.
The CoreValve TAVR delivery system, showing the valve partially deployed.
March 17, 2015 — New two-year data from the CoreValve U.S. Pivotal High Risk Study, which demonstrated superior two-year survival benefits from transcatheter aortic valve replacement (TAVR) using the Medtronic CoreValve system compared to surgical aortic valve replacement (SAVR) in high-risk patients with severe aortic stenosis. The CoreValve study is the first head-to-head study to show statistically significant survival differences favoring TAVR in aortic stenosis patients who are considered high-risk for surgery. Results were presented as a late-breaking clinical trial at the American College of Cardiology (ACC) 2015 meeting.
“Survival is statistically better with TAVR and sustained at two years,” said Michael Reardon, M.D., professor of cardiothoracic surgery at Houston Methodist DeBakey Heart and Vascular Center, and chairman of the patient screening committee of the CoreValve U.S. Pivotal Trial. “We found that the survival advantage actually increases for TAVR — that the absolute difference in all-cause death rates between the two groups has widened, with 4.8 percent more people surviving with TAVR than surgery at one year and 6.4 percent more surviving with TAVR at two years.”
With these latest findings, Reardon sees reason to revisit current guidelines.
“This trial moves the field forward in that ACC/AHA guidelines state that TAVR is a reasonable alternative to surgical valve replacement in high-risk patients, as judged appropriate by the heart team,” he said. “This trial’s data suggest that TAVR with the self-expanding valve should be the preferred treatment in patients with symptomatic severe aortic stenosis at increased risk from surgery.”
Acknowledging that these are early findings, he said that longer follow-up is needed to confirm that this valve continues to demonstrate benefits over surgery. The CoreValve High Risk trial will follow patients for five years.
Two-year outcomes from the study found that the rate of all-cause mortality was significantly lower in TAVR patients than in the SAVR patients (22.2 percent vs. 28.6 percent, p=0.04), with the absolute difference in all-cause mortality increasing between the two groups from 4.8 percent at one year to 6.5 percent at two years. The CoreValve U.S. Pivotal High Risk Trial randomized patients with a heightened risk of death from open-heart valve replacement to TAVR or the standard surgical procedure. Death rates at one year were significantly lower for the 390 TAVR patients than for the 357 patients who had open-heart surgery. Year two data include three more patients, two of whom received a smaller second-generation CoreValve that was not available earlier.
“In this trial CoreValve maintains a low and stable stroke rate and the recovery advantages CoreValve demonstrated at one year are maintained at two years. Current ACC/AHA guidelines refer to TAVR as a reasonable alternative to SAVR in high risk patients as judged by the heart team; however, these clinical data suggest a change in these guidelines may be warranted for the self-expanding valve in this patient population,” Reardon said. “Further, I believe that the results of this randomized study suggest that self-expanding transcatheter valve therapy should be considered standard of care and preferred over surgery in this patient population.”
Using robust prospective evaluation, the rate of stroke was significantly lower in the TAVR group as compared to the SAVR group at two years (10.9 vs. 16.6 percent, p=0.05), and the major stroke rates were comparable (6.8 vs. 9.8 percent; p=0.25). The combined endpoint of all-cause mortality or major stroke significantly favored the TAVR group (24.2 vs. 32.5 percent, p=0.01).
Rates of major adverse cardiovascular and cerebrovascular events (MACCE) at one year were still superior at two years and were statistically lower in the TAVR group than the SAVR group (29.7 vs. 38.6 percent, p=0.01). While the echocardiographic parameters of effective orifice area and mean aortic-valve gradient remained stable for both groups over the two-year period, the TAVR group showed superior hemodynamics compared with the surgical group time points during the clinical trial follow-up (p=<0.001). Moderate to severe paravalvular regurgitation (PVL) for the TAVR group at two years (6.1 percent) proved consistent with the low one-year rate.
“Durability is an issue, and we saw no evidence of TAVR valve deterioration,” Reardon said. “Effective valve orifice and mean pressure gradients [measures of valve quality] were statistically superior with TAVR at every time point during the trial.”
Surgery Still Leads in Reducing Paravalvular Leak
Leaking around the new valve is one area where surgery consistently performs better than TAVR in clinical trials.
“Moderate to severe paravalvular leakage with TAVR was low at one year at 6 percent and stayed low at two years at 6.1 percent,” Reardon said, noting that, unlike some other TAVR studies, leaks have not had an impact on mortality with this valve. “We had very few cases of moderate or more leaks, and this may be why we don’t see a mortality signal with leakage.”
CoreValve High Risk Study
The CoreValve High Risk Study randomized 747 severe aortic stenosis patients at 45 centers in the United States to treatment with either the CoreValve System or open-heart surgery. The patients were estimated to have a predicted risk of operative mortality of 15 percent or higher at 30 days, assessed by two clinical site surgeons and confirmed by at least two surgeons on a National Screening Committee. The average age of patients in the study was 83.2 years old, and the study enrolled a nearly equal number of men and women. In addition to the STS predicted risk of mortality estimate of 7.4 percent, these patients had documented co-morbidities, frailty and disability that placed them at increased risk for surgery.
The CoreValve System was approved by the U.S. Food and Drug Administration (FDA) in 2014 for patients at extreme-risk and high-risk for surgery.
This clinical trial was funded by Medtronic. Reardon serves on Medtronic’s advisory board but receives no personal funding from the company.
For more information: acc.org, www.medtronic.com