TAVR continues to be comparable to surgery in patients at low surgical risk
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Key takeaways:
- TAVR had similar clinical outcomes compared with surgery at 4 or 5 years in low-risk patients with severe aortic stenosis.
- Hemodynamic parameters suggested the TAVR valves remained durable at 4 or 5 years.
SAN FRANCISCO — In patients with severe aortic stenosis at low surgical risk, transcatheter aortic valve replacement was linked with similar long-term outcomes to surgery, according to two trials presented at TCT 2023.
In addition, neither of the TAVR valves studied in the PARTNER 3 trial and the Evolut Low Risk Trial had unfavorable hemodynamic results compared with surgical valves.
PARTNER 3
For the PARTNER 3 trial of 1,000 patients (mean age, 73 years) with severe aortic stenosis at low surgical risk, researchers randomly assigned patients to receive TAVR with a balloon-expandable valve (Sapien 3, Edwards Lifesciences) or surgical AVR. The results were simultaneously published in The New England Journal of Medicine.
At 5 years, the first primary endpoint of death, stroke or rehospitalization for HF, a device-related reason or a procedure-related reason occurred in 22.8% of the TAVR group compared with 27.2% of the surgery group (difference, –4.3 percentage points; 95% CI, –9.9 to 1.3; P = .07), Martin B. Leon, MD, professor of medicine and chief innovation officer and director of the Cardiovascular Data Science Center for the Division of Cardiology at Columbia University Irving Medical Center, and founder of the Cardiovascular Research Foundation, said during a press conference.
Five-year rates for the individual components of the first primary outcome were as follows: death, 10% in the TAVR group vs. 8.2% in the surgery group (HR = 1.23; 95% CI, 0.79-1.9); stroke, 5.8% vs. 6.4% (HR = 0.87; 95% CI, 0.51-1.48); and rehospitalization, 13.7% vs. 17.4% (HR = 0.75; 95% CI, 0.54-1.05).
Leon said the difference in mortality rate was driven by non-CV mortality, and the researchers consider it to be a play of chance.
The second primary endpoint was a composite of death, disabling stroke, nondisabling stroke and number of rehospitalization days at 5 years, assessed using a win ratio analysis. The win ratio was 1.17 (95% CI, 0.9-1.51; P = .25), with TAVR winning 22.1% of the time and surgery winning 19% of the time, Leon said.
The TAVR group had higher rates of valve thrombosis (2.5% vs. 0.2%; HR = 10.52; 95% CI, 1.37-80.93), but lower rates of serious bleeding (10.2% vs. 14.8%; HR = 0.65; 95% CI, 0.45-0.95) and similar rates of new pacemaker implantation (TAVR, 13.5%; surgery, 10.4%; HR = 1.33; 95% CI, 0.9-1.96) compared with surgery, the researchers reported.
Importantly, Leon said, 5-year rates of bioprosthetic valve failure did not differ between the groups (TAVR, 3.3%; surgery, 3.8%; HR = 0.86; 95% CI, 0.42-1.77; P = .69).
“The event rates were quite low and similar among the two therapies,” he said.
At 5 years, mean valve gradient was 12.8 mm Hg in the TAVR group and 11.7 mm Hg in the surgery group (P < .001), according to the researchers.
As a result of the findings, “we can tell our patients who have low-risk aortic stenosis that with these two therapies, by the end of 5 years there is more than a 70% chance that they will be alive and feeling well, with either no or very mild symptoms,” Leon said. “We can also tell them that at the end of 5 years, there is more than an 85% chance with either therapy that they would be alive with a durable heart valve based on [bioprosthetic valve failure] assessment.”
Evolut Low-Risk Trial
The Evolut Low-Risk Trial included 1,414 patients (mean age, 74 years) with severe aortic stenosis at low surgical risk (STS PROM: TAVR group, 2%; surgery group, 1.9%) who were randomly assigned to TAVR with a self-expanding valve (CoreValve, Evolut R or Evolut PRO, Medtronic) or to surgical AVR. The results were simultaneously published in the Journal of the American College of Cardiology.
The primary outcome of all-cause mortality or disabling stroke at 4 years occurred in 10.7% of the TAVR group vs. 14.1% of the surgery group (HR = 0.74; 95% CI, 0.54-1; P = .05), Michael J. Reardon, MD, Allison Family Distinguished Chair In Cardiovascular Research, professor of cardiovascular surgery in the Academic Institute and full member in the Research Institute at Houston Methodist and Weill Cornell Medical College, said during the press conference.
The absolute difference in the rate of the primary outcome between groups increased over time, from –1.8% at 1 year to –2% at 2 years to –2.8% at 3 years to –3.4% at 4 years, Reardon said.
“We all know that TAVR has an early advantage over surgery, but the real question is: Is this durable?” Reardon said. “Now, for the first time, we see something not only holding up but actually increasing in favor of TAVR.”
At 4 years, the rate of all-cause mortality was 9% in the TAVR group vs. 12.1% in the surgery group (P = .07) and disabling stroke was 2.9% vs. 3.8% (P = .32). The composite of all-cause mortality, disabling stroke or aortic valve rehospitalization was 18% in the TAVR group vs. 22.4% in the surgery group (P = .04).
New permanent pacemaker implantation at 4 years was higher in the TAVR group (24.6% vs. 9.9%; P < .001), the researchers found.
Mean gradient at 4 years was better in the TAVR group (9.8 mm Hg vs. 12.1 mm Hg; P < .001), as was effective orifice area (TAVR, 2.1 cm2; surgery, 2 cm2; P < .001), according to the researchers.
There were no significant differences at 4 years in rates of reintervention, valve thrombosis, valve endocarditis or moderate or worse paravalvular regurgitation.
Reardon said during the press conference that no conclusions should be drawn about how the two TAVR valves compare to each other, because the trials were not designed that way.
“The intrinsic risk levels of both of these trials were different,” he said. “We treated the higher end of low risk; they treated the lower end of low risk. We do have different patient populations, so it’s very hard to speculate, and really scientifically invalid, to compare my valve against the PARTNER valve. That’s not the way these trials work.”
References:
- Reardon MJ, et al. Late-breaking clinical trials: Session I, in collaboration with The New England Journal of Medicine. Presented at: TCT Scientific Symposium; Oct. 23-26, 2023; San Francisco (hybrid meeting).
- Forrest JK, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.09/813.
- Mack MJ, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2307447.
Perspective
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We have data showing that TAVR is an excellent therapy for patients who are at low surgical risk. When we have conversations with patients about whether to have surgery or TAVR, we have to be honest and say that while the short to medium range data looks for TAVR, we really need to know what things will look like 10 years from now in terms of whether TAVR is remaining comparable to surgery. But even with that discussion, particularly depending on the age of the patient, patients are generally going to go with the less-invasive approach.
When making this decision, we also have to look at the patient’s individual anatomy and make sure we can get a good result with TAVR. Not every patient will get a great result with TAVR, and a lot of those patients were excluded from these two studies. We have to be careful about taking these data and saying they apply to all low-risk patients. There are some patients who would not have made it into these studies because they had severe calcification, bicuspid valve disease, etc. That is a much more nuanced conversation that we have to have with those patients.
Perspective
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Thomas E. MacGillivray, MD
Cardiothoracic surgeons welcome randomized evidence in low-risk patients to help inform clinical decision-making in the management of aortic stenosis from a position of clinical and scientific equipoise. However, as the clinical application of TAVR to lower-risk cohorts is considered, 10-year outcomes are really needed prior to selecting TAVR for patients outside of those studied in the two low-risk trials.
These considerations are important as surgeons and cardiologists weigh the best choices for patients:
• The recent STS National Database benchmark has established that the survival following over 42,000 patients with isolated low-risk surgical AVR was 92.9% at 5 years and nearly 90% at 8 years when inclusion criteria were matched to those used in the low-risk trials.
• Other registry and trial data have raised concerns with TAVR outcomes in lower-risk patients once follow-up surpasses 5 years.
• Valve intervention such as TAVR is most commonly an isolated procedure in clinical practice, yet in both the PARTNER 3 and Evolut Low Risk trials, a quarter of the surgical comparator groups had concomitant procedures such as CABG, which are well known to be associated with reduced short-term and long-term outcomes.
• Patients studied in PARTNER 3 and Evolut Low Risk had a mean age of 73 years, had normal ejection fraction, and had trileaflet aortic valve stenosis. As such, these data do not represent younger patients or those with bicuspid anatomy.
• Cardiac surgery after TAVR, including TAVR explant, has become the fastest-growing operation in the U.S. over the last 5 years.
For these reasons, the valvular practitioner and the heart team may wish to exercise caution before translating the recent reports of highly selected cohorts from PARTNER 3 and Evolut Low Risk into clinical practice until longer-term data, and data from isolated procedural cohorts, are made available.
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Leon MB, et al. Late-breaking clinical trials: Session I, in collaboration with The New England Journal of Medicine. Presented at: TCT Scientific Symposium; Oct. 23-26, 2023; San Francisco (hybrid meeting).
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