April 2, 2014 — The key trial presented at the 2014 American College of Cardiology (ACC), which will likely be the one attendees will remember “they were there for” in the years to come, was data showing transcatheter aortic valve replacement (TAVR) outperformed surgical valve replacement. The late-breaking presentation of the CoreValve U.S. pivotal high-risk trial showed the Medtronic self-expanding CoreValve device had a 26 percent survival benefit above the surgical valve implant patients.
This data was a major topic of discussion at ACC, as the operators using the CoreValve only had three proctored cases to learn how to use the device prior to performing their fourth and subsequent TAVR procedures that counted toward the trial. In comparison with this high-level of inexperience with the new procedure, most of the cardiac surgeons performing the open-heart valve replacements had a decade or more of experience with their procedures. The minimally invasive nature of TAVR combined with this revelation will set transcatheter valve replacement on its way to becoming the standard of care, replacing surgeries in the years to come if future trials continue to reflect the positive mortality trend.
“There was a 26 percent improvement in mortality for TAVR, which I think was probably the most provocative finding,” said David Adams, M.D., professor and chairman of the department of cardiothoracic surgery, Mount Sinai Medical Center, New York, and co-principal investigator of the study. “This difference in advantage toward TAVR was pretty much unanticipated by all of us involved.”
When Adams first heard about transcatheter valves he thought they were impractical and would never work effectively, let alone beat surgical outcomes. “I remember saying as a surgeon ‘this could never work’ — that calcium is going to go everywhere and everyone is going to have a mortality or stroke,” Adams said. “That didn’t happen. Then we got to where it was better than medical therapy and then that it was equivalent to surgery. Now it might be superior to surgery.”
Simplicity of TAVR Procedures
Most pivotal trials for new cardiology devices show a learning curve due to the inexperience of the operators using a new and unfamiliar device. Usually operators improve outcomes over time after using the device or a new technique for 20 to 50 cases. This was not seen in this trial, suggesting the CoreValve procedure is easy to master since the initial outcomes were very positive.
“None of our sites in the trial had ever used a TAVR device before,” Adams said. “We each got three roll-in patients and then started keeping score. It shows this is a learnable procedure and it is not something that takes four to five years to learn.”
The trial enrolled patients with an assessed increased risk of death from aortic valve surgery. Of 795 patients randomly assigned to valve replacement by catheter or surgery, 747 patients underwent one of the procedures: 390 in the TAVR arm and 357 in the surgical aortic valve replacement arm. The average age was about 83 years in both groups. The results exceeded the initial non-inferiority goal and, by pre-design, then moved on to a superiority analysis. Death rates at 30 days were not significantly different, with a 3.3 percent death rate for TAVR and 4.5 percent for surgery. A significant difference emerged at the one-year primary endpoint of all-cause mortality: 14.2 percent for TAVR with CoreValve compared with 19.1 percent for surgical replacement.?
“This is the first prospective study of any device that suggests TAVR is superior to [surgery] in a predefined population of patients, and that’s a provocative finding,” Adams said. “The low mortality rates with conventional surgery far exceeded the predicted mortality according to the Society of Thoracic Surgeons predictive model. In order to pass a superiority threshold, transcatheter treatment with the CoreValve device had to exceed excellent surgical outcomes.”
Exploratory analyses also showed the one-year rate for heart attack, stroke or related death was significantly lower for TAVR at 20.4 percent compared with 27.3 percent for surgical replacement.
“We also performed multiple different subgroup analyses for one-year death rates and found the survival benefit of TAVR with CoreValve was consistent across all clinical subgroups we examined, regardless of thresholds,” Adams said.
The 30-day observed death rates for TAVR and surgical valve replacement were much lower than the anticipated rate of 15 percent, Adams said, suggesting that the patient population may have had lower risks than intended. In addition to the STS score, frailty and other disabilities were considered in the evaluation of risk. Randomization ensured a robust trial nonetheless, he said, adding that this study confirmed that current risk assessment models, including expert physician reviews, overestimate contemporary surgical risks.
A potential limitation of the study is the higher dropout rate for patients randomly assigned to surgery, as reported with previous TAVR trials. Forty patients assigned to surgery dropped out of the study before treatment, while only four assigned to the TAVR arm dropped out. The trial was designed with this anticipated attrition rate, and a sensitivity analysis confirmed that there were no significant differences in the risk profiles between patients who underwent the assigned surgical treatment and those who withdrew, Adams said.
“We are confident that the higher withdrawal rate in the surgical arm did not affect our findings,” he said.
Strong results from the other arm of CoreValve’s U.S. pivotal trial with patients at extreme risk for standard aortic valve replacement surgery were reported in October and led to U.S. Food and Drug Administration (FDA) approval for the device in this population.
Questions Remain for Use in Low-Risk Patients
Adams said there are two key issues that data will need to address prior to transcatheter valves being considered for use in low-risk patient populations — regurgitation and durability. Although very positive, Adams said there is still an incidence of valve regurgitation that needs to be addressed before these valves can be considered for less sick patients.
“We have got to solve the issue with regurgitation,” he explained. “The rate is small at 6.1 percent moderate and severe regurgitation, but that number needs to be 3 to 4 percent to really move into use with lower-risk patients.”
Durability of these devices will be reported as more patient data is accumulated over the years after implantations, Adams said. Final follow-up results from the CoreValve CE pivotal study were also presented at ACC.14, which demonstrated excellent long-term durability at four years in patients with severe aortic stenosis. The study also showed significant improvements in quality of life at one year, which were sustained through four years, with 74 percent of patients improving at least one New York Heart Association (NYHA) functional class from baseline to four years. Additionally, the rates of regurgitation and stroke remained low, with 83 percent of patients free from stroke at four years follow-up.
Differences Between Balloon and Self-Expanding Valves
The CoreValve became the second transcatheter aortic valve to gain FDA clearance in January. It is the first self-expanding valve. The first FDA-cleared transcatheter aortic valve was the balloon-expandable Edwards Sapiens. There has been a lot of discussion in recent years as to whether the balloon-expandable or self-expanding approach will be superior for patient outcomes.
A first-ever randomized head-to-head comparison of these two devices presented at ACC.14 found balloon-expandable valves result in more successful procedures and relieve symptoms more frequently than self-expanding valves. The study tracked 241 transcatheter valve-replacement procedures in five major hospitals in Germany. Half of the patients received a balloon-expandable valve, and the other half received a self-expanding valve.
Procedures using a balloon-expandable valve had a success rate of 95.9 percent as compared to 77.5 percent for the self-expanding valve. Patients receiving the balloon-expandable valve also reported improvements in symptoms 30 days after the procedure at a rate of 94.3 percent compared to 86.7 percent in patients receiving a self-expanding valve. This was mainly due to lower amounts of regurgitation, possibly due to the balloon being able to better seat the valve in the aortic annulus.
However, operators in Europe and the United States have pointed to positive attributes in both devices that may favor use in one patient over another.
“One day in the field we will take off the blinders and you will not be in the self-expanding camp or the balloon-expandable camp,” Adams said. “I am so sure there is going to be some patients who are going to benefit from self-expanding and some patients who will benefit from balloon expanding valves.”