WASHINGTON - A first in transcatheter aortic valve replacement trials, the CoreValve prosthesis was superior to surgical valve replacement in patients with severe aortic stenosis at increased surgical risk, showing a significantly lower risk of mortality 1 year later.

In the U.S. CoreValve High Risk Study, a prospective randomized controlled study of almost 800 patients, the rate of all-cause mortality at 1 year, the primary endpoint, was 14.2% among those in the transcatheter aortic valve replacement (TAVR) group, compared with 19.1% among those in the surgery group, a statistically significant difference that represented a 26% survival benefit at 1 year for the CoreValve, Dr. David H. Adams reported at the annual meeting of the American College of Cardiology.

This is the first prospective, randomized study to show superiority for transcatheter valve therapy over surgery, and "there's no study or trial that I'm aware of that's suggested that TAVR patients would have a superior survival outcome," Dr. Adams of Mount Sinai Medical Center, New York, said in an interview. Based on these results, he said he expects that TAVR "will increasingly become the alternative of choice for patients" at this level of risk.

The study was the high-risk arm of the U.S. CoreValve pivotal trial. The CoreValve self-expanding prosthesis was approved in January 2014 by the Food and Drug Administration for use in extreme risk patients, based on the results of the extreme risk cohort of patients. The data from the study in the high-risk trial are being reviewed at the FDA, according to the manufacturer, Medtronic.

The study compared the safety and effectiveness of TAVR with the CoreValve device to surgical valve replacement in 795 patients at 45 U.S. centers. The patients had severe aortic stenosis, had New York Heart Association class II heart failure or higher, and were judged to have at least a 15% risk of death within 30 days after surgery and less than a 50% risk of death or irreversible complications within 30 days after surgery. Their mean age was about age 83 years, almost half were females, most had class NYHA class III HF, and cardiac risk factors included coronary artery disease (in about two-thirds), previous coronary artery bypass surgery (about 30%), a previous MI (about 25%), and almost all had heart failure.

At 1 year, a composite of major adverse cardiovascular and cerebrovascular events (death from any cause, MI, any stroke, or reintervention), a secondary endpoint, was significantly lower among those on TAVR (20.4%) vs. the surgical group (27.3%). The rate of any stroke at 30 days was 4.9% in TAVR patients and 6.2% in the surgical group; and at 1 year, those rates were 8.8% and 12.6%, respectively; neither difference was statistically significant. Major vascular complications and permanent pacemaker implantations were significantly higher in the TAVR group (22.3% at 1 year, vs. 11.3% in the surgical group). In the TAVR group, there were five cases of cardiac perforation; there were no perforations in the surgical group.

Patients are being followed through 5 years. The 2-year mortality data are encouraging, with continued separation of the all-cause mortality curves, although the numbers are still small, Dr. Adams said.

More patients in the trial refused surgical valve replacement after randomization and the mortality rate within 30 days after surgery was 4.5%, which was lower than the rate specified for inclusion in the study, which was 15% or higher, so the patients may have been at a lower risk than planned, he said.

During the discussion, the inevitable comparisons to the results of the Placement of Aortic Transcatheter Valves A (PARTNER A) study were raised. In PARTNER A, which compared the safety and effectiveness of the balloon-expandable SAPIEN Transcatheter Heart Valve to aortic valve replacement surgery in high-risk patients with severe symptomatic aortic stenosis, found no difference in mortality between the two arms and an increase in cerebrovascular events in the TAVR arm.

Dr. Adams said that different characteristics of the device in the two trials are possible explanations as to why the TAVR results were superior to surgery in the CoreValve study, and not in PARTNER A. "The size of the catheter as well as perhaps the self-expanding nature of the device both could help explain that," he said.

While patient risk was assessed differently in the studies, and the Society of Thoracic Surgeons scores of the patients were different, "we're confident these were patients at increased risk for surgery," he added.

The study was published simultaneously in the New England Journal of Medicine on March 29 (2014 March 29 [doi:10.1056/NEJMoa1400590]).

The study is funded by the CoreValve manufacturer, Medtronic. Dr. Adams disclosed receiving grant support from Medtronic during the conduct of the study and other support from Medtronic and Edwards Lifesciences outside the submitted work.

emechcatie@frontlinemedcom.com

TAVR beat surgery in high-risk aortic stenosis patients