TAVR With Evolut: Interim Results Promising in Low-Risk Patients

March 16, 2019

NEW ORLEANS — Transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis (CoreValve, Evolut R, or Evolut PRO, Medtronic) was noninferior to surgical aortic valve replacement in an interim Bayesian analysis of the primary endpoint — death from any cause or disabling stroke at 24 months — in a new trial involving patients with severe aortic stenosis at low surgical risk.

"TAVR may be a preferred strategy to surgery in patients with severe aortic stenosis at low risk of surgical mortality," coauthor Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, Texas, told theheart.org | Medscape Cardiology

The study is to be presented Sunday, March 17, at the American College of Cardiology 68th Annual Scientific Session (ACC) 2019 by Reardon and simultaneously published in The New England Journal of Medicine (NEJM). Because of an embargo break the information has been allowed be reported early and published online in NEJM.

TAVR has previously been shown to be superior to surgery in patients at high surgical risk and to be noninferior to surgery in patients at intermediate survival risk. As a result, the procedure has been endorsed for patients at increased risk for surgical complications, and the number of TAVR interventions performed in the United States has now surpassed the number of isolated surgical aortic valve replacements, the study authors note in the NEJM paper.

But use of TAVR in patients at low surgical risk requires compelling evidence of safety and effectiveness given the low mortality and stroke incidence with aortic valve surgery in relatively young and healthy patients, they add.

"For this study we are looking at patients at low surgical risk — these make up 80% of the population treated for aortic stenosis, so they represent a very big piece of the pie, and about half of these patients could be candidates for TAVR," Reardon told theheart.org | Medscape Cardiology

"These interim results show that the TAVR procedure easily met noninferiority for the Bayesian-predicted primary endpoint in low-risk patients. Also, 30-day results show TAVR was substantially safer than surgery at 30 days.  And 1-year results suggest TAVR is superior to surgery in terms of all-cause mortality/disabling stroke and CHF [congestive heart failure] hospitalization. Mortality and disabling stroke were very low across the board," Reardon said. 

Hemodynamics were also better with TAVR, and patient-prosthetic mismatch, where the valve is too small for the patient's needs, was also less, he noted. "While regurgitation was higher with the TAVR procedure, only a small percentage of patients received the third-generation valve, which has an added skirt to reduce perivalvular leak, so regurgitation rates should come down as use of this device increases," he added.

"Based on this data, I would say TAVR is the preferred therapy in this group," Reardon concluded. 

He reported that currently around 60,000 TAVR procedures are performed each year in the United States. If the intermediate-risk group is fully implemented, this could increase to 75,000; if the low-risk indication is approved, this is likely to expand to 100,000 or more.

For the current trial, researchers randomly assigned 1468 patients at low surgical risk (<3% estimated risk for 30-day death with surgery) to TAVR or surgery, with either procedure attempted in 1403 patients. The mean age was 74 years.

Most patients in the TAVR group received the second-generation Evolut R device, with 22% getting the third-generation Evolut Pro.

At this prespecified interim analysis, 12-month follow-up was available for 432 patients in the TAVR group and 352 patents in the surgery group. Data from 24-month follow-up were available for 72 TAVR patients and 65 surgery patients.

The 24-month estimated incidence of the primary endpoint (death or disabling stroke) was 5.3% in the TAVR group vs 6.7% in the surgery group (Bayesian probability of noninferiority > .999).

At 30 days, TAVR patients had a lower incidence of disabling stroke (0.5% vs 1.7%), bleeding complications (2.4% vs 7.5%), acute kidney injury (0.9% vs 2.8%), and atrial fibrillation (7.7 % vs 35.4%) and a higher incidence of moderate or severe aortic regurgitation (3.5% vs 0.5%) and pacemaker implantation (17.4% vs 6.1%).

Mortality rates were very low: At 1 year, death rates were 0.4% in the TAVR group vs 1.2% in the surgery group (nonsignificant). Twelve-month data also show a numeric (but statistically nonsignificant) lower rate of all-cause mortality and disabling stroke in the TAVR group (2.9% vs 4.6%), a significant reduction in disabling stroke (0.8% vs 2.4%), and a significant reduction in heart failure hospitalization (3.2% vs 6.5%).

In addition, Reardon presented a nonprespecified triple endpoint at 1 year of death, disabling stroke, or heart failure hospitalizations showing a significant reduction with TAVR (5.6% vs 10.2%; P = .002).

At 12 months, TAVR patients also had superior hemodynamics with lower aortic valve gradients (8.6 mm Hg vs 11.2 mm Hg) and larger effective orifice areas (2.3 cm2 vs 2.0 cm2).  

A second trial on TAVR in patients at low surgical risk (PARTNER 3) showed similar promising results with a different valve device, Edwards Lifescience's SAPIEN 3. The findings are also to be presented at the same Late Breaking Clinical Trial session at the ACC.19. The embargo on this trial was similarly broken; the trial is covered by theheart.org | Medscape Cardiology and has also been published online in NEJM.   

Further discussion from the meeting on the implications of the two trials will be covered in a follow- up theheart.org | Medscape Cardiology news article.

The current study was supported by Medtronic. Reardon sits on an advisory board for Medtronic.

American College of Cardiology 68th Annual Scientific Session (ACC) 2019. To be presented March 17, 2019.

 N Engl J Med. Published online March 16, 2019. Full text

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