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Atlanta — A randomized transcatheter aortic valve replacement (TAVR) trial demonstrated that a self-expanding device performs better on multiple prognostically important measures of valve function at 1 year than a balloon-expandable device.

In this head-to-head comparison in patients with severe aortic stenosis and a small aortic annulus, TAVR using the self-expanding valve was noninferior to the balloon-expandable device on clinical outcomes and superior on bioprosthetic valve dysfunction (BVD) at 12 months.

Based on the advantage for prognostic markers, "we expect to see better outcomes for those who received the self-expanding device in about 3-4 years," reported the principal investigator Howard C. Herrmann, MD, section chief, interventional cardiology, Hospital of the University of Pennsylvania, Philadelphia.

The trial was unusual in that 87% of the 716 patients enrolled in 13 countries were women. This reflects the entry criterion of an aortic valve annulus area of < 430 mm².

Trial Compares Devices in Small Annuli

Previously published observational evidence has suggested that the self-expanding supra-annular Evolut (Medtronic) device is associated with better hemodynamics than the intra-annular balloon-expanding Sapien (Edwards Lifesciences), Hermann noted.

He explained that the decision to test this potential difference in a study primarily enrolling women is based on evidence that good hemodynamics might be especially important when the aortic annulus is small.

By enrolling a predominantly female population, this multinational trial, called SMART, also provided an opportunity to focus on outcomes in a group typically underrepresented in interventional trials overall and TAVR trials in particular, Hermann added.

"It is important to looked specifically at this group because women present differently than men and are at greater risk of complications after surgery or TAVR," said Hermann, noting women are currently the recipients of about 40% of TAVR devices.

The postmarketing study with a planned 5-year follow-up was conducted in North America and Europe. The all-comer design permitted entry to those with bicuspid aortic valves.

The 1 year outcomes of the SMART trial were presented as a late-breaking clinical trial session at the annual meeting of the American College of Cardiology (ACC) and simultaneously published in The New England Journal of Medicine.

More than 80% of patients at baseline were hypertensive, and about 40% were in class III or higher heart failure. The median age was 80 years.

Of the two co-primary endpoints evaluated at 1 year, the first was a composite of mortality, disabling stroke, and heart failure hospitalization. For this endpoint, the comparison was performed on the basis of noninferiority.

The second primary endpoint was a composite of hemodynamic structural valve dysfunction (HSVD; mean gradient ≥ 20 mmHg), nonstructural valve dysfunction (NSVD; prosthesis-patient mismatch or ≥ moderate total aortic regurgitation), clinical valve thrombosis, endocarditis, and need for aortic valve reintervention. This comparison was performed on the basis of superiority.

If both co-primary endpoints were met, numerous secondary endpoints were also compared on the basis of superiority.

On the primary event endpoint, the percentage of patients with an event was numerically lower for those randomized to the self-expandable device (9.4% vs 10.6%). Noninferiority was confirmed with a high degree of statistical significance (P < .001).

For the primary composite hemodynamic endpoint, the lower rate of valve dysfunction (9.4% vs 41.6%) among those randomized to the self-expanding value was highly significant (P < .001) for superiority.

Valves Differ Markedly for 12-Month HSVD

Within the composite hemodynamic endpoint, the advantages, if any, were small for the self-expanding device in regard to thrombosis (3.3% in both arms), aortic valve reintervention (0.9% vs 0.6%), and endocarditis (0.6% vs 2.3%). Rather, the advantages for the self-expanding device were concentrated in HSVD (3.2% vs 32.2%) and NSVD (5.9% vs 18.2%).

By meeting the two co-primary endpoints, secondary endpoints could be explored. Most of these were lower among those randomized to the self-expanding device by a significant margin. This included moderate to severe prosthesis-patient mismatch (10.3% vs 35.1%; P < .001) and mean gradient (7.7 vs 15.7 mmHg; P < .001).

BVD, compared only in female study participants, was also lower by a wide margin (8.4% vs 41.8%; P < .001).

Device success at 30 days, defined by level 2 of the Valve Academic Research Consortium, was higher in the self-expanding device arm (85.2% vs 59.2%; P < .001). However, procedure time (116 vs 106 minutes; P = .002) and contrast volume use (121 vs 95 mL; P < .001) were also greater with the self-expanding valve.

Safety outcomes, including valve embolization, kidney injury, coronary artery obstruction, and hospital readmissions, did not differ between the two groups at 3- or 12-month intervals. The higher rate of pacemaker implant among those randomized to the self-expanding device (14.0% vs 9.3%; P = .051) did approach statistical significance.

The overall advantages of the self-expanding TAVR device are expected to translate into lower rates of TAVR failure over the next several years, Hermann said.

Predominantly Female TAVR Trial Important

The ACC-invited discussant Suzanne J. Baron, MD, director of Interventional Cardiology Research, Mass General Hospital, Boston, called SMART a "really important trial for a couple of reasons."

In addition to the fact that it is the largest randomized trial to directly compare two TAVR devices, she called the number of women included in this trial "astounding."

"This study is really going to provide us with a rich data with which we can really explore and confirm the benefit of TAVR in our female patients," she said.

Based on the evidence that hemodynamics matters, she also expects that long-term outcomes will favor the self-expanding device, but she cautioned that this result is not assured.

"I will be very interested to see how the long-term follow-up goes with the SMART trial," Baron said. She pointed out that the median age of the trial participants was 80 years, introducing "a competing risk of death" that might dilute the differences over long-term follow-up.

"It will be important to see if we can detect the differences in outcome that we are expecting," she said.

Hermann reported financial relationships with Abbott Vascular, Boston Scientific, Edwards Lifesciences, Highlife Med, Innovative, Shockwave, and Medtronic, which makes the self-expanding Evolut TAVR device and provided funding for the SMART trial. Baron had financial relationships with Abiomed, Acarix, Boston Scientific, Edwards Lifesciences, Medtronic, Shockwave, and Zoll Medical. She was not involved in the design or management of the SMART trial.

Ted Bosworth is a medical journalist based in New York City.