SENTINEL: Embolic protection device for use during TAVR safe, but efficacy not yet proven

WASHINGTON — Although a transcatheter embolic protection device was safe, the primary endpoints of the SENTINEL study were not met, according to a presentation at TCT 2016.

“Prior exploratory studies with embolic protection using a dual filter system during TAVR have shown a reduction in new cerebral lesion volume demonstrated by MRI,” Susheel Kodali, MD, from Columbia University Medical Center, said at a press conference.

Researchers randomly assigned 363 patients undergoing TAVR at 19 centers to receive the transcatheter embolic protection device (Sentinel, Claret Medical) as part of a safety arm (n = 123), to receive the device and undergo imaging (n = 121) or to receive no device and undergo imaging (n = 119). All patients were assessed immediately after the procedure, at 30 days and at 90 days. Those in the imaging arms underwent 3-T diffusion-weighted brain MRI at 2 to 7 days and at 30 days.

Susheel Kodali

The primary safety endpoint was MACCE, defined as death, stroke or acute kidney injury at 30 days, while the primary efficacy endpoint was a comparison of the two imaging arms in reduction in median new lesion volume in protected brain territories on MRI scans between 2 and 7 days.

Captured debris was analyzed, and patients underwent a series of neurocognitive assessments.

The rate of MACCE in the device groups was 7.3%, which was non-inferior to the historical performance goal of 18.3% (P for noninferiority < .001) and was not statistically different from the control group (9.9%; P = .41).

New lesion volume was greater in the control group than in the device imaging group, but the difference was not statistically significant (178 mm³ vs. 102.8 mm³; reduction, 42%; P = .33), according to the researchers, who simultaneously published their findings in the Journal of the American College of Cardiology.

However, after adjustment for potential cofounders, there was a significant reduction in new lesion volume in protected territories associated with embolic protection (P = .02).

At 30 days, the rate of stroke was 9.1% in controls vs. 5.6% in the device arms (P = .25), which was not statistically significant because the study was not powered for clinical endpoints, Kodali said.

The device captured embolic debris in almost all patients who received it (99%), including thrombus, calcification, valve tissue, artery wall and foreign material, according to the researchers.

There were no significant differences between the groups in neurocognitive decline, but the researchers observed a relationship between lesion volume and neurocognitive decline (P = .0022).

“Until more rigorous efficacy evidence is obtained, the choice to use neuroprotection during TAVR requires a risk-benefit analysis, considering the unpredictable risk and consequences of strokes, the demonstrated safety of the therapy and the perception of therapeutic benefits,” Kodali said during the press conference.

In a related editorial published in JACC, Azeem Latib, MD, and Matteo Pagnesi, MD, both from the interventional cardiology unit, San Raffaele Scientific Institute, Milan, Italy, wrote that “the small imaging sample size is probably the main reason the SENTINEL study is negative, but this does not equate to saying that there is no role for [cerebral embolic protection].

“We are dealing with a potential benefit that cannot be ignored as TAVR shifts to younger and lower-risk patients, where preventing procedure-related cerebral injury remains a significant unmet clinical need with potentially important long-term sequelae,” they concluded. – by Dave Quaile

References:

Kodali SK, et al. Late-Breaking Clinical Trials 3. Presented at: TCT Scientific Symposium; Oct. 29-Nov. 2, 2016; Washington.

Kapadia SR, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.10.023.

Latib A, Pagnesi M. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.10.036.

Disclosure: The study was funded by Claret Medical. Kodali reports receiving research funding from Abbott, Boston Scientific, Claret Medical, Direct Flow Medical, Edwards Lifesciences and Medtronic; being on the steering committee for trials funded by Claret Medical and Edwards Lifesciences; and receiving consultant fees, honoraria or speakers’ bureau fees from Dura Biotech, Thubrikar Aortic Valve Inc. and VS Medical. Latib and Pagnesi report their institution has participated in trials of embolic protection devices funded by Claret Medical, Innovative Cardiovascular Solutions and Keystone Heart.