Low-risk TAVR trials represent ‘historic moment’ in care of aortic stenosis
NEW ORLEANS — Transcatheter aortic valve replacement — already a mainstay of treatment for intermediate- and high-risk patients with severe aortic stenosis — may soon become the preferred therapy for low-risk patients as well.
Two studies presented at the American College of Cardiology Scientific Session — the PARTNER 3 and Evolut Low Risk trials — showed that the procedure, with two different valves, is not only comparable to, and in some aspects better than, surgery in terms of safety and efficacy.
“What we’re seeing here is a class effect of TAVR, and we have to recognize it as such,” Michael J. Reardon, MD, professor and Allison Family Distinguished Chair of Cardiovascular Research at Houston Methodist Hospital, said after his presentation of the Evolut Low Risk study. “We’ve been seeing it creep up on as we’ve moved to treating lower-and-lower-risk patients. This procedure is evolving and improving at such a rapid rate that it’s hard to imagine what we’re going to see 5 years from now.”
In the international, multicenter PARTNER 3 trial, which was simultaneously published in The New England Journal of Medicine, 1,000 patients (mean age, 73 years) with severe aortic stenosis and a mean Society of Thoracic Surgeons risk score of 1.9% were randomly assigned to TAVR with a balloon-expandable valve (Sapien 3 system, Edwards Lifesciences) or surgical aortic valve replacement.
“There has been strong evidence supporting TAVR in defined patient cohorts, but PARTNER 3 is designed to really answer the important question of the relative value and importance of the procedure in a low-surgical-risk cohort,” Martin B. Leon, MD, 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, said during his presentation of the trial.
At 1 year, the rate of the primary endpoint of a composite of death, stroke or rehospitalization in the TAVR group was nearly half that of the surgery group (8.5% vs. 15.1%; P < .001 for noninferiority; HR = 0.54; 95% CI, 0.37-0.79; P = .02 for superiority).
One-year mortality was also lower with TAVR vs. surgery (1% vs. 2.5%; HR = 0.41; 95% CI, 0.14-1.17), as were the rates of all stroke (1.2% vs. 3.1%; HR = 0.38; 95% CI, 0.15-1), death or disabling stroke (1% vs. 2.9%; HR = 0.34; 95% CI, 0.12-0.97) and rehospitalization (7.3% vs. 11%; HR = 0.65; 95% CI, 0.42-1).
The treatment effect was clearly preserved in the intention-to-treat population and there was no heterogeneity across subgroups, Leon noted.
In terms of secondary endpoints, TAVR compared with surgery was associated with a lower rate of stroke (P = .02) and lower rates of death or stroke (P = .01) and new-onset atrial fibrillation (P < .001) at 30 days. The index hospitalization time was also shorter with TAVR (P < .001) and the risk for a poor treatment outcome, including death or a low Kansas City Cardiomyopathy Questionnaire score (P < .001), at 30 days was lower with TAVR.
Additionally, patients who underwent TAVR had a more rapid 30-day functional recovery based on 6-minute walk tests and other self-reported quality-of-life measures.
“Functional assessments of early recovery favor TAVR at 30 days, but they essentially equalize at 12 months,” Leon said.
Major vascular complications, new permanent pacemaker insertions or moderate or severe paravalvular regurgitation did not differ significantly between treatment groups. Mild paravalvular regurgitation, however, was with surgery vs. TAVR.
“Based upon these findings, TAVR, through 1 year, should be considered the preferred therapy in low-surgical-risk aortic stenosis patients,” Leon said. “The choice of TAVR vs. surgery in aortic stenosis patients should be a shared-decision making process, respecting patient preferences, understanding knowledge gaps, especially in younger patients, and considering clinical and anatomic factors.”
More follow-up is still necessary, though, he added, and patients in this trial will be followed for 10 years.
Evolut Low Risk Trial
Similarly, results from the Evolut Low Risk Trial, which was also published simultaneously in NEJM, showed promise for the use of TAVR with a self-expanding supra-annular bioprosthesis (CoreValve, Evolut R or Evolut PRO; Medtronic) in patients with severe aortic stenosis who are at low surgical risk.
In the international, multicenter, prospective, noninferiority trial, Reardon and colleagues randomly assigned 1,468 low-risk patients (mean age, 74 years) with severe aortic stenosis to TAVR or surgery and used a Bayesian adaptive design that prespecified an “early-win” interim analysis when 850 patients reached 1-year follow-up, and prespecified criteria for success was posterior probability > 0.972.
The primary endpoint was a composite of all-cause mortality or disabling stroke at 2 years.
“Knowing that we were moving into a low-risk population and it might be hard to convince some people, we wanted to use endpoints that were objective and impactful since this was essentially an open-label trial,” Reardon said.
The 24-month estimated incidence of the primary endpoint was lower for the TAVR group vs. the surgery group and met the criteria for noninferiority (5.3% vs. 6.7%; posterior probability of noninferiority > 0.999).
At 30 days, patients who underwent TAVR compared with surgery had lower incidences of disabling stroke (0.5% vs. 1.7%), life-threatening or disabling bleeding (2.4% vs. 7.5%), acute kidney injury (0.9% vs. 2.8%) and AF (7.7% vs. 35.4%). Average hospital stay was also shorter with TAVR than surgery (6.2 vs. 2.6 days).
However, patients who underwent TAVR had higher incidences of moderate or severe aortic regurgitation (3.5% vs. 0.5%) and pacemaker implantation (17.4% vs. 6.1%).
At 12 months, aortic valve gradients were lower in the TAVR group (8.6 mm Hg vs. 11.2 mm Hg) and effective orifice areas were larger (2.3 cm2 vs. 2 cm2). Rates of major stroke and all-cause mortality were also lower with TAVR at 12 months, but the differences were not statistically significant.
Also at 1 year, Kaplan-Meier curves were lower for TAVR vs. surgery for all-cause mortality or disabling stroke (2.7% vs. 4.6%) and HF hospitalizations (3.1% vs. 6.4%).
Additionally, procedural time and hospital stay after the procedure were significantly shorter with TAVR than with surgery.
Notably, Reardon said, prosthesis-patient mismatch at 1 month and 1 year were significantly better with TAVR than surgery.
NYHA functional class and KCCQ scores improved more with TAVR vs. surgery at 30 days, but they were comparable at 1 year.
“At 1 year, both groups had excellent survival. TAVR showed fewer disabling strokes and HF hospitalizations with superior hemodynamics manifest by lower gradients and larger effective orifice areas, and as we move into low-risk patients, I think effective orifice area will be critical,” Reardon said.
During a discussion following the presentations, Eugene Braunwald, MD, professor of medicine at Harvard Medical School and a Cardiology Today Editorial Board member, called the presentation of the PARTNER 3 and Evolut Low Risk trials a “historic moment.”
“We should all recognize this and are going to tell our grandchildren and great grandchildren about the time these incredible advances in care of patients with aortic stenosis were presented,” he said. – by Melissa Foster, with additional reporting by Katie Kalvaitis and Erik Swain
Leon M, et al.
Reardon MJ, et al. Joint American College of Cardiology/New England Journal of Medicine Late-Breaking Clinical Trials. Both presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosures: PARTNER 3 was funded by Edwards Lifesciences. Leon reports he has received research support from Abbott, Boston Scientific, Edwards Lifesciences and Medtronic; he has received consulting fees from Abbott, Boston Scientific, Gore, Medtronic, Meril Life Sciences; and he is the co-principal investigator of the PARTNER 3 trial. The Evolut Low Risk Trial was funded by Medtronic. Reardon reports he has received consultant fees paid to his institution from Medtronic.