March 15, 2019
PARTNER 3 Compares TAVR and Surgery in Low-Risk Patients With Severe Symptomatic Aortic Stenosis
March 16, 2019—The American College of Cardiology (ACC) announced that the 1-year findings from the PARTNER 3 trial will be presented on March 17 by Martin B. Leon, MD, at the ACC's 68th Annual Scientific Session, being held March 16–18 in New Orleans, Louisiana. The findings have been published online ahead of print by Michael J. Mack, MD, et al in The New England Journal of Medicine.
According to the ACC, the study found that transcatheter aortic valve replacement (TAVR) using the Sapien 3 valve (Edwards Lifesciences) among patients with severe, symptomatic aortic stenosis who were at low surgical risk significantly reduced the primary endpoint of death, stroke, and rehospitalizations by 46% at 1 year compared with conventional surgery. The rates of death from any cause, stroke, and repeat hospitalizations independently favored TAVR versus surgery at 30 days (4.2% vs 9.3%; P = .002) and at 1 year (8.5% vs 15.1%; P =.001).
Dr. Leon, the Lead Investigator of the study, is Director of the Center for Interventional Vascular Therapy at New York-Presbyterian/Columbia University Irving Medical Center, Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons in New York, New York. The study was funded by Edwards Lifesciences.
In the ACC announcement, Dr. Leon commented, “This is a landmark study because it involves 80% of the people who are currently being treated with surgery for aortic stenosis. Our hope was that TAVR would be noninferior or comparable to surgery, and we were surprised to find an almost 50% reduction in the primary endpoint, from 15.1% in the surgical group to 8.5% with TAVR. This is beyond anything we could have expected, mostly because surgery is so good in treating aortic stenosis in these low-risk patients.”
As noted in the ACC announcement, PARTNER 3 is the fifth randomized trial of the PARTNER series of studies, which collectively includes more than 9,000 patients with severe aortic stenosis.
PARTNER 3 was composed of 1,000 patients with severe aortic stenosis at 71 centers in the United States and several other countries. More than 95% of patients were enrolled at United States sites. Patients were carefully screened to be low risk for either TAVR or surgery and were randomly assigned to receive the Sapien 3 TAVR device, the company's newest-generation technology, or surgical valve replacement.
The ACC reported that compared with the earlier PARTNER trials with intermediate- and high-risk surgical patients, this low-risk group was younger (average age, 73 years), had fewer comorbid conditions, and had fewer symptoms. There were also more men than women enrolled (67.5% vs 32.5%).
The primary endpoint was the combined 1-year rate of all-cause death, any stroke, and rehospitalizations (those related to the valve, the procedure, or heart failure).
Dr. Leon noted, “Taken by themselves, each component of the primary endpoint also favored TAVR, which is confirmatory evidence of the outcome.”
The 1-year rates of adverse events for TAVR versus surgery, respectively, were:
- Mortality, 1% vs 2.5% (P = .09)
- Stroke, 1.2% vs 3.1% (P = .04)
- Rehospitalization, 7.3% vs 11% (P < .05)
Several secondary endpoints included length of hospital stay (3 days vs 7 days). Patients in the TAVR group also had more rapid 30-day functional recovery based on 6-minute walk tests and other self-reported quality-of-life measures. Postoperative or new onset atrial fibrillation rates also favored TAVR (5% vs 40%). Major vascular complications were similar between the groups, as was the need for new permanent pacemakers (6.5% vs 4%).
However, the incidence of new left bundle block was higher with TAVR, which may be a predictor of needing a new pacemaker in future. Moderate or severe paravalvular leaks, leaks around the valve, were similar in the two groups.
Dr. Leon commented, “Surgery eventually catches up to TAVR in terms of functional recovery and quality of life, but it takes several months. TAVR is a less invasive procedure, so we expect an earlier return to normal daily activities compared with surgery. There has also been an evolution of TAVR technology, increased operator experience, and enhanced procedural techniques, all of which combine to lower complications after TAVR especially in the lowest risk patients.”
He stated further, “The results of this trial in low-risk patients indicates that the choice of TAVR versus surgery for severe aortic stenosis should be independent of surgical risk profile assessments. The combined rate of death and disabling stroke at 1 year was only 1% with TAVR, which was an unexpectedly favorable outcome. Based on these findings, the choice of TAVR versus surgery should be a shared decision-making process that respects patient preferences and considers some of the knowledge gaps, especially in treating young patients.”
ACC stated that there are two major limitations to the PARTNER 3 trial. First, the data are limited to 1-year follow-up and longer-term follow-up is needed to be certain that the TAVR devices are as durable as surgical valves—the patients in this trial will be followed for 10 years. Second, certain patients were excluded in this study, such as patients with bicuspid aortic valve disease and those with poor anatomy that prevented transfemoral access for the valve.