WASHINGTON, D.C.—The FDA skipped convening an expert panel after release of positive results for the CoreValve Extreme Risk cohort and later approved the device. Will it do the same for CoreValve as a treatment for patients who are considered at high surgical risk, based on findings presented March 29 at the American College of Cardiology scientific session in Washington, D.C.?
At one year, high-risk patients treated with the CoreValve transcatheter aortic valve replacement (TAVR) had a mortality rate of 14.2 percent compared with 19.1 percent for counterparts treated with conventional open-heart surgery. “Patients who were treated with the CoreValve device had a 26 percent improvement in survival at one year,” said David H. Adams, MD, of Mount Sinai Medical Center in New York City, at the late-breaking clinical trials. “This result was highly significant.”
The U.S. CoreValve High Risk study was a randomized controlled clinical trial designed to assess the safety and efficacy of the CoreValve (Medtronic) device in patients with severe aortic stenosis who have a 15 percent or higher risk of death within 30 days of surgery, as determined by a heart team. The primary endpoint was the death rate at one year. The secondary clinical endpoint was major adverse cardiovascular and cerebrovascular events at 30 days and one year. Medtronic funded the study.
The trial randomized 390 patients to TAVR treatment and 357 to surgical aortic valve replacement between February 2011 and September 2012. Forty-five centers in the U.S. participated in the study, which kicked off the late-breaking clinical trials at ACC.14.
Participants had a mean age of 83.2 years and 52.7 percent were men. About 56 percent had a score on a comorbidity index that reflected a severe burden of illness. The CoreValve group had a lower mortality rate in as-treated and intention-to-treat analyses.
“In terms of the primary endpoint of all-cause mortality, this passed both the noninferiority and superiority thresholds in the as-treated and intention-to-treat cohorts,” Adams said. “The absolute risk reduction was 4.9 percent in the as-treated cohort and 4.8 percent in the intention-to-treat cohort.”
One limitation Adams acknowledged was that patients in the trial had a lower mortality rate than the 15 percent or less specified in the study inclusion criteria. “The trial population may have been at lower risk than was intended,” he said.
Discussant Michael J. Mack, MD, of Baylor Health Care System in Plano, Texas, and a member of the executive committee of the PARTNER trial, said that comparisons between the two trials are “inevitable.” PARTNER evaluated the safety and effectiveness of the Sapien (Edwards Lifesciences) TAVR valve in inoperable and high risk patients with severe aortic stenosis. Positive results from studies in the two patient populations allowed for FDA approval of Sapien.
In early January, the FDA approved the CoreValve device for extreme risk patients, making it the second commercially available TAVR device in the U.S. The FDA had announced after results from the extreme risk trial were unveiled at TCT.13 that it had decided to not convene an expert panel.
Mack highlighted differences between the two trials, including predicted risk in the inclusion criteria. “In PARTNER, it was 11 percent, so it seems to me that this is more an intermediate risk group of patients than a high risk group of patients,” Mack said.
Adams expressed confidence in their identification of patients at increased risk. “This risk is a paradigm. I am not sure where you set the lines anymore. We sort of know small, medium and large; trying to divide that into four or five is becoming harder now.”
The results simultaneously were published online March 29 in the New England Journal of Medicine.