Use of a cerebral embolic protection (CEP) device did not lead to a lower risk of stroke or mortality in patients undergoing transcatheter aortic valve replacement (TAVR) patients, according to new trial data. However, the CEP device did have a significant effect on the incidence of periprocedural stroke in transcatheter aortic valve replacement (TAVR) for the treatment of aortic stenosis, the study’s lead author emphasized. Findings from the 3,000-patient PROTECTED TAVR trial were reported Saturday at Transcatheter Cardiovascular Therapeutics (TCT) 2022 in Boston and published simultaneously online in The New England Journal of Medicine. The prospective post-market trial set out to assess whether the capture of debris by the Sentinel Cerebral Embolic Protection System (Boston Scientific) may reduce the risk of stroke, after previous studies have shown mixed results. “An analysis by the Society of Thoracic Surgeons–American College of Cardiology Transcatheter Valve Therapy Registry showed that after commercial approval of the CEP device, approximately 13% of TAVR procedures included the use of such a device. A larger randomized trial of CEP during TAVR that includes clinical stroke as an end point would be relevant to health care providers and patients,” noted the authors, led by Samir R. Kapadia, MD, from the Cleveland Clinic. Speaking at TCT, Kapadia noted that the objective of the PROTECTED TAVR trial was “fairly straightforward” in investigating whether clinical stroke in transfemoral TAVR is reduced with use of CEP, across all risk groups and all commercially available devices. Study setup The PROTECTED TAVR trial enrolled a total of 3,000 patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group) at 51 centers across North America, Europe and Australia between February 2020 and January 2022. The primary endpoint was clinical stroke within 72 hours after TAVR or before discharge – whichever came first, said Kapadia, noting that, noting that disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. Of the patients assigned to the CEP group, a CEP device was successfully deployed in 94.4% - 1406 of the 1489 patients in whom an attempt was made. “The patients in the trial were generally representative of the overall population eligible for TAVR with CEP,” said the authors, noting an average patient age of 78.9 years, and a mean Society of Thoracic Surgeons surgical risk score, of 3.4%. “The demographic and clinical characteristics of the patients at baseline and the procedural characteristics were generally similar in the two trial groups, with the exception of a higher percentage of female patients in the CEP group than in the control group (42.0% vs. 37.8%),” they added. Key findings Kapadia and colleagues reported that the incidence of clinical stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% [34 of 1501 patients] vs. 2.9% [43 of 1499]; −0.6% difference; 95% confidence interval [CI], −1.7 to 0.5; P=0.30). However, the lead researcher noted that when secondary endpoints of stroke type were considered, there was a significantly lower incidence of disabling stroke in the CEP group (0.5%) versus the control (1.3%), with an overall difference of -0.8% (95% CI: -1.5, -0.1; p=0.02). Furthermore, he noted that most of the reduction in disabling strokes was driven by a lower incidence of ischemic stroke (17% control vs. 6% CEP). There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site, the study reports. Furthermore, subgroup analyses performed in the trial did not show a specific population that might benefit from selective CEP use or any procedural factors potentially associated with a benefit from CEP use (e.g., type of anesthesia, valve type, and balloon dilation before or after valve implant), said the team. They concluded that although the trial did not definitively identify a role for CEP in all patients undergoing TAVR, the CEP device was safe and may be a reasonable choice for some patients and physicians. “The ultimate decision regarding the use of a CEP device during TAVR should be based on careful discussions between caregivers and patients about the risks and benefits and should incorporate personalized interpretation of the data from this and other trials of CEP, as well as other factors, including device cost,” they said. A serious blow? Writing in an accompanying editorial commentary, John D. Carroll, MD, from the University of Colorado School of Medicine, Anschutz Medical Campus, and Jeffrey L. Saver, MD, from David Geffen School of Medicine at UCLA, suggested that the results from the current trial may change the use of the CEP device in practice. “Until now, the clinicians who use the device have been influenced by seeing retrieved debris with the expectation of an associated clinical benefit, which has not been confirmed by the primary end-point results of the current trial,” they said, noting that some clinicians may continue to use CEP devices because of its safety and the suggestion that it prevents disabling strokes, while others could hesitate at the prospect of adding a major cost to TAVR procedures without a proven clinical benefit. “As a whole, this trial strikes a serious blow to the hope that this first CEP device would have a definitive effect in the prevention of TAVR-related strokes,” said the editorialists, noting that the ‘smoking gun’ of captured debris was not associated with high-quality evidence of stroke prevention. “The safety of the device and its possible effect on disabling strokes provide a ray of hope, but the concern persists that CEP, approved and marketed on the basis of surrogate outcomes, may not actually provide a clear and incontestable clinical benefit,” they warned. Sources: Kapadia SR, Makkar R, Leon M, et al. Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement. N Engl J Med. 2022 Sep 17. Carroll JD, Saver JL. Does Capturing Debris during TAVR Prevent Strokes? N Engl J Med. 2022 Sep 17. Image Credit: Jason Wermers/CRTonline.org