NEW ORLEANS — Transcatheter aortic valve replacement (TAVR) safely treated severe aortic stenosis even in low-risk patients and, depending on the device used, may yield results that are on par with or better than what is achieved with surgical aortic valve replacement (SAVR), two trials showed.
TAVR with the Sapien 3 resulted in significantly fewer combined deaths, strokes, and rehospitalizations at 1 year (8.5% vs 15.1% for surgery, P<0.001 for non-inferiority and P=0.001 for superiority), according to Kaplan-Meier estimates from the PARTNER 3 team led by Michael Mack, MD, of Baylor Scott and White Health Heart Hospital in Plano, Texas.
Separately, in a prespecified interim analysis of the Evolut Low Risk Trial, the rate of combined deaths and disabling strokes at 24 months was 5.3% for TAVR with Medtronic’s line of self-expanding bioprostheses and 6.7% with surgery. Noninferiority was met with a margin of 6% for efficacy (posterior probability of noninferiority >0.999) but not superiority (posterior probability of superiority 0.779), Jeffrey Popma, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues reported.
Both late-breaking trials — featuring the lowest-risk TAVR patients studied to date, both with an average surgical mortality risk score of 1.9% — were released early due to an embargo break before presentation here at the American College of Cardiology’s annual meeting and publication in the New England Journal of Medicine.
“Both studies are real game-changers in the way we’re going to be treating patients with severe aortic stenosis,” commented Howard Herrmann, MD, of Philadelphia’s Penn Heart and Vascular Center.
“These trials will result in approval of TAVR for low-risk patients,” he said in a phone interview.
PARTNER 3 Trial
People were eligible for the PARTNER 3 trial if their Society of Thoracic Surgeons (STS) Predicted Risk of Mortality score was less than 4%.
“The proof-of-concept first case of TAVR performed by Cribier and colleagues in 2002 was intended to open a treatment pathway for the highest-risk patients with limited therapeutic options. Our findings in low-risk patients suggest that the value of TAVR, as compared with surgery may be independent of risk profiles,” the investigators said.
Mack’s team wound up having 1,000 patients randomized to the Sapien 3 (a third-generation balloon-expandable bioprosthesis from Edwards Lifesciences) or a surgical valve. The mean age was 73 years.
Among these patients, all three individual components of the primary efficacy endpoint at least numerically favored TAVR over SAVR:
- All-cause death: 1.0% vs 2.5% (HR 0.41, 95% CI 0.14-1.17)
- Stroke: 1.2% vs 3.1% (HR 0.38, 95% CI 0.15-1.00)
- Rehospitalization: 7.3% vs 11.0% (HR 0.65, 95% CI 0.42-1.00)
The incidence of new-onset atrial fibrillation at 30 days was substantially lower with TAVR (5.0% vs 39.5%, HR 0.10, 95% CI 0.06-0.16).
Complications seen more with TAVR than surgery, as in previous trials, included major vascular complications (2.2% vs 1.5%), new permanent pacemaker insertions (6.6% vs 4.1%), moderate or severe paravalvular regurgitation (0.8% vs 0%), and coronary-artery obstruction (0.2% vs 0.7%).
Yet surgical patients in the trial showed lower mean aortic valve gradients at 30 days (11.2 vs 12.8 mm Hg) and ended up with a lower risk of left bundle branch block at 1 year (8.0% vs 23.7% for TAVR, HR 3.43, 95% CI 2.32-5.08).
“The most important limitation of this trial is that our current results reflect only 1-year outcomes and do not address the problem of long-term structural valve deterioration,” according to the authors. “In this trial involving younger, low-risk patients, the protocol requires clinical and echocardiographic follow-up to continue for at least 10 years.”
Evolut Low Risk Trial
The Evolut study enrolled patients with no more than 3% STS predicted mortality risk, who were 74 years old on average. The TAVR cohort had received the self-expanding CoreValve, Evolut R, or Evolut PRO bioprostheses.
As individual components of the 24-month primary endpoint, mortality came out 4.5% for both TAVR and SAVR groups, whereas disabling strokes appeared to favor TAVR (1.1% vs 3.5%; -2.3 percentage point difference, 95% CI for difference -4.8 to -0.4).
Importantly, the preliminary analysis was handled with adaptive Bayesian design once 850 patients out of 1,468 completed 12-month follow-up. Despite the primary endpoint being at 2 years, only 137 had gotten their 24-month data into the trial at the time of the manuscript’s preparation.
Regardless, 30-day death rates were generally “very low” (0.5% for TAVR and 1.3% for SAVR; P=not significant) as mortalities were largely fewer than expected, Popma’s group noted.
TAVR had the upper hand in the 30-day composite safety outcome counting death, disabling stroke, life-threatening bleeding, major vascular complication, and stage 2 or 3 acute kidney injury (5.3% vs 10.7%; -5.4 percentage point difference, 95% CI for difference -8.3 to -2.6), as well the individual components of life threatening bleeding, acute kidney injury, and atrial fibrillation.
Hospitalizations for heart failure at 12 months were also down with the transcatheter procedure (3.2% vs 6.5%; -3.4 percentage point difference, 95% CI -5.9 to -1.0).
However, this group showed more moderate or severe aortic regurgitation at 30 days (3.5% vs 0.5%). At 12 months, these patients went onto have lower aortic valve gradients (8.6 mm Hg vs 11.2 mm Hg) and bigger effective orifice areas (2.3 cm2 vs 2.0 cm2).
Pacemaker implants were also more frequent in the 30 days after TAVR (17.4% vs 6.1%; +11.3 percentage point difference, 95% CI 8.0-14.7), but a new permanent pacemaker did not significantly correlate with more deaths at 12 months among those who survived to discharge (3.4% vs 1.2%), Popma and colleagues said.
The investigators acknowledged the lack of blinding in their endpoint adjudication process. Like the PARTNER 3 group, they plan for continued follow-up over 10 years.
“One thing that is inevitable is people are going to start to compare the devices,” Herrmann suggested. But there are no glaring differences that would make operators choose one over the other between Sapien and Evolut — except perhaps the higher pacemaker rate observed in PARTNER 3, he said.
The Evolut Low Risk Trial was supported by Medtronic.
PARTNER 3 was funded by Edwards Lifesciences.
Mack disclosed grants from Edwards Lifesciences for the study and other ties to Medtronic, Abbott, and Gore.
Popma reported grants from Medtronic for the study and other grants and/or personal fees from Edwards Lifesciences, Boston Scientific, and Abbott Vascular.