In the 3,000-person PROTECTED TAVR trial, the sentinel dual-filter system did not produce a significant reduction in perineural strokes compared with no-device controls (2.3% vs. 2.9%, P=0.30), according to Samir Kapadia, MD, from the Cleveland Clinic. Kapadia added that no subgroup appeared to have fewer strokes with protected TAVR. “Stroke remains unpredictable,” he said in a presentation at the Transcatheter Cardiovascular Therapeutics (TCT) meeting organized by the Cardiovascular Research Foundation. The results were published simultaneously in the New England Journal of Medicine (NEJM). This may be disappointing to clinicians who hoped to narrow down CEP candidates based on this test. It had been thought that by valve anatomy or procedural characteristics, some patients would benefit at least more than others, Robert Cubeddu, MD, of the Naples Heart Institute in Florida, commented at a TCT news conference. There was some redemption in the association of Sentinel with fewer disabling strokes after TAVR (0.5% vs. 1.3%, P=0.02), with the number needed to treat to prevent a disabling stroke being 125 patients. But this is not a definitive finding and should be replicated, cautioned John Carroll, MD, of the University of Colorado School of Medicine/Anschutz Medical Campus in Aurora, and Jeffrey Saver, MD, of the David Geffen School of Medicine at the University of California, Los Angeles. , in an NEJM editorial. Otherwise, the trial produced no substantial differences in mortality rates or in the combined endpoint of stroke, transient ischemic attack or delirium. The incidence of acute kidney injury was the same at 0.5% between groups. PROTECTED TAVR comes years after the much smaller SENTINEL trial, in which CEP successfully filtered histopathological debris in 99% of patients but failed to significantly reduce the volume of new lesions in protected brain regions or reduce major adverse cardiac and cerebrovascular events events. But the FDA approved Sentinel in 2017 on the premise that catching debris before it reaches the brain would theoretically benefit patients undergoing endocardial procedures. Since approval, however, real-world data continue to show no stroke benefit with the device. CEP adoption has been variable and slow to proliferate. When asked how the new data would affect clinical practice at the press conference, the panelists broke out into a few laughs. Michael Young, MD, of Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire, said the study “muddies the waters for programs that are more mid-volume. A number needed to treat 125 will be a tough sell for some. of these programs to use it everywhere for all their patients.” “A lot goes into cost and we have to be realistic about that,” Cubeddu said. “In many [TAVR] programs across the country, the margins for sustainability and cost and revenue are just marginal.” He suggested that it would be interesting to see how the Centers for Medicare & Medicaid Services (CMS) interpret the PROTECTED TAVR results. Post-market testing was conducted at 51 centers in North America, Europe and Australia. Investigators randomized transfemoral TAVR candidates to the procedure with or without CEP. Neurological examinations were performed in all patients at baseline and after TAVR. Routine neuroimaging was not performed to detect occult cerebral infarction. Participants were on average 78.9 years old. There was a greater proportion of women in the protected group (42.0% vs. 37.8% of controls), while the Society of Thoracic Surgeons surgical risk was similar between groups (3.4% vs. 3.3%). Sentinel deployed successfully in 94.4% of attempts. The primary endpoint of the trial was stroke within 72 hours after TAVR or before discharge. Carroll and Saver cautioned that the study’s count of these events may have been flawed. “Underdetection of stroke events may have occurred because neurological assessments were not always performed by experienced neurologists and because a formal structured interview was not used to determine the presence of stroke symptoms. A small overcount of endpoint events may also have occurred due to the use of a nonstandard approach to classifying asymptomatic occult infarcts as strokes,” they wrote. In terms of safety, only one patient had a vascular complication at the access site, according to Kapadia. “The safety of the device and its potential effect on disabling strokes provide a glimmer of hope, but the concern remains that CEP, approved and marketed based on surrogate outcomes, may not actually provide a clear and unequivocal clinical benefit’, Carroll and Saver. In any case, PROTECTED TAVR may be a testament to how much TAVR has matured since it was first developed in 2002. “The fact that the study’s negative results were partly due to the low incidence of stroke in the control group conveys good news — the incidence of non-CEP stroke is low in modern practice compared with early experience with TAVR, and is likely due to operator experience, technical improvements in procedural equipment, and the use of TAVR in healthier patients,” the authors reported.
Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow along
Revelations PROTECTED TAVR was funded by Boston Scientific. Kapadia disclosed relationships with Navigate and Admedus. Carroll disclosed relationships with Edwards LifeSciences and Medtronic. Saver has disclosed relationships with and/or support from Filterlex, Abbott, Medtronic, Bayer, Roche, Johnson & Johnson, Amgen, MIVI, Rapid Medical, Novo Nordisk and Edwards. Cubeddu has disclosed no industry affiliations. Young disclosed a relationship with Medtronic.
