SNOWMASS, COLO. – The Food and Drug Administration has approved the first-ever U.S. randomized clinical trial of transcatheter aortic valve replacement versus open surgical replacement in low–surgical risk patients with symptomatic severe aortic stenosis.
The PARTNER III trial will enroll roughly 1,200 patients age 65 or older, all with a Society of Thoracic Surgeons risk score of less than 4%, at 50 sites beginning this spring, Dr. Vinod H. Thourani said at the Annual Cardiovascular Conference at Snowmass.
Dr. Vinod H. Thourani
This is a noninferiority trial with a primary endpoint comprising a 1-year composite of death, stroke, or rehospitalization. The study is sponsored by Edwards Lifesciences, and patients randomized to transcatheter aortic valve replacement (TAVR) will receive the company’s low-profile Sapien 3 valve.
Coprincipal investigators are Dr. Michael J. Mack of the Baylor Health Care System in Plano, Tex., and Dr. Martin B. Leon of Columbia University, New York. Dr. Thourani is a member of the PARTNER III executive committee.
This is a study that could upend clinical practice, he observed.
“Are we going to have within the next 5 years 80%-90% of all patients who present with severe symptomatic aortic stenosis treated with transcatheter valves? We’re really at a major crossroads here, I believe,” said Dr. Thourani, professor of surgery and medicine and codirector of the structural heart and valve center at Emory University in Atlanta.
He ran down the numbers: Today, roughly 80% of all surgical aortic valve replacements (SAVR) in the United States are performed in low–surgical risk patients. These low-risk patients comprise roughly 65% of the total operable population with severe aortic stenosis. If PARTNER III and other data show that TAVR provides results comparable to SAVR in this group, Dr. Thourani predicted that it’s likely most low–surgical risk patients will opt for the less invasive approach. The appeal is no surgical incision, less pain, a shorter or no ICU stay, and faster return to normal activity.
Right now, U.S. and European guidelines state that TAVR is the preferred or alternative strategy to SAVR only in the relatively small group comprised of inoperable or high–surgical risk patients. In clinical practice, TAVR has already supplanted SAVR in the 10% of operable patients with high surgical risk. And TAVR is poised to do so in the roughly 25% of patients who fall into the intermediate–surgical risk category, according to the cardiothoracic surgeon.
He predicted that the 1-year outcomes of TAVR in more than 1,000 intermediate-risk participants in the PARTNER II trial will create a stir when presented this year, as a late-breaker at the annual meeting of the American College of Cardiology in Chicago. Although he stressed that he doesn’t know the results, the 30-day outcomes presented at last year’s Transcatheter Cardiovascular Therapeutics conference are extremely promising: a 1.1% all-cause mortality rate in patients with an average Society of Thoracic Surgeons risk score of 5.3%, for a stunning observed-to-expected ratio of just 0.21. Plus, a 1.0% rate of disabling stroke in this large multicenter randomized experience.
“That becomes really compelling data for us to think we’re ready now to go to the next step,” Dr. Thourani said. “My belief is at the rate we’re going, we’ll see most intermediate-risk patients going to TAVR.”
To date there has been only one randomized trial of TAVR versus SAVR in low–surgical risk patients: the Nordic Aortic Valve Intervention Trial (NOTION), which included 280 randomized patients with an average Society of Thoracic Surgeons risk score of 3%.
In the 2-year results presented by Dr. Lars Søndergaard of the University of Copenhagen at TCT 2015, all-cause mortality was 2.1% with TAVR and 3.7% with SAVR at 30 days, 4.9% with TAVR and 7.5% with SAVR at 12 months, and 8.0% versus 9.8% at 24 months. The 30-day rates of major bleeding, cardiogenic shock, atrial fibrillation, and acute kidney injury were all substantially lower in the TAVR group. All very impressive. However, Dr. Thourani found the TAVR patients’ pacemaker-requirement rate troubling. At 30 days post TAVR, 34% of patients had a pacemaker, compared with 1.6% of the SAVR group. By 24 months, 41% of the TAVR group had received a pacemaker, compared with just 4% of the SAVR group.
“What’s the acceptable pacemaker rate for someone utilizing TAVR – 5%, 10%, 40%? That’s something we as a community have to look at,” the surgeon observed. He noted that his purchase price for a TAVR valve is roughly $32,500, whereas a SAVR valve costs him $4,500. And at Emory, putting in a pacemaker costs an added $10,000-$15,000 for the device.