The British Heart Foundation's BHF PROTECT-TAVI trial has delivered disappointing results for cerebral embolic protection during transcatheter aortic valve implantation (TAVI), finding no evidence that the device reduces stroke risk. The findings, presented at the American College of Cardiology (ACC) 2025 Scientific Session and simultaneously published in the New England Journal of Medicine, represent the second major setback for embolic protection technology.
The trial randomized 7,635 patients with aortic stenosis to undergo TAVI with or without the Sentinel cerebral embolic protection device (Boston Scientific). After a blinded analysis, the study was stopped for futility when no significant differences emerged between treatment groups.
Key Trial Findings
Stroke within 72 hours of TAVI or before discharge occurred in 2.1% of patients assigned to embolic protection and 2.2% of patients treated without the device (RR 0.99; 95% CI 0.73 to 1.34). The rate of severe stroke was identical between groups at 0.5%.
"This trial testing the routine use of cerebral embolic protection during TAVI does not confirm any evidence of reduction in the risk of stroke," said lead investigator Dr. Rajesh Kharbanda from Oxford University Hospitals NHS Foundation Trust.
The researchers conducted extensive subgroup analyses stratified by age, sex, bicuspid valve anatomy, clinical risk score, valve type, and extent of aortic valve calcification, but found no benefit in any population.
Disabling stroke within 6 to 8 weeks after TAVI occurred in 1.2% of patients treated with embolic protection and 1.4% of those in the control group (RR 0.89; 95% CI 0.60-1.31), a non-significant difference that contrasts with PROTECTED TAVR, which had shown a reduction in disabling stroke.
Clinical Implications
The BHF PROTECT-TAVI results, combined with the earlier PROTECTED TAVR trial, now encompass more than 10,000 randomized patients showing no clear benefit from routine embolic protection.
"It's better in the basket than in the brain, for sure. I think all of us are disappointed that the two big trials now have failed to show a benefit in the clinical endpoint of stroke," said Dr. S. Chris Malaisrie from Northwestern University Feinberg School of Medicine during the press conference.
Dr. Jay Giri from the University of Pennsylvania, who wasn't involved in the study, noted that he has used embolic protection in approximately 75% of TAVI cases in recent years but expects that percentage to decline.
"Unfortunately, it does appear that we may have potentially spent a lot of time and money on an intervention that doesn't have clear clinical efficacy," Giri told TCTMD.
Device Performance and Limitations
The Sentinel device was successfully deployed in 81.2% of patients randomized to embolic protection, with at least one filter fully deployed in 87.5% of patients. This success rate was lower than the 95% reported in PROTECTED TAVR, raising questions about real-world effectiveness.
Dr. Samir Kapadia, who led PROTECTED TAVR, questioned whether the lower deployment rate might have affected outcomes, though Dr. Kharbanda emphasized that the intention-to-treat analysis remains the gold standard and that the deployment rate reflects routine clinical practice.
Several theories have emerged about why the device fails to show clinical benefit despite capturing debris:
- Device pores may be too large to prevent all emboli
- Incomplete seal around filter edges
- Protection of only two of the three main cerebral vessels
- Possibility that the device itself causes as many events as it prevents
Declining Usage Patterns
A recent analysis published in JACC: Cardiovascular Interventions showed that embolic protection use in the US had already declined following PROTECTED TAVR, from 13.5% to 10.2% of TAVI procedures.
Dr. David Cohen from St. Francis Hospital believes usage will decline further: "Routine use is hard to justify in 2025."
Financial considerations may accelerate this trend. Dr. Giri noted that as many as 30% of US hospitals are "margin negative" for TAVI, and eliminating embolic protection could help these centers improve their financial position.
Future Directions
Despite the negative findings, some experts believe embolic protection may still have a role in specific scenarios. Dr. Raj Makkar from Cedars Sinai Medical Center suggested the device might be beneficial in cases requiring aortic leaflet modification, such as Basilica procedures or when using leaflet splitters, where substantial embolic debris can be released.
Dr. Kharbanda remains optimistic about the concept: "Stroke is still very clinically relevant, and we need to identify strategies that are going help us. We need to understand whether there are specific groups of patients that might benefit and that's going to need further trials."
Many experts are calling for professional societies like the ACC and the Society for Cardiovascular Angiography and Interventions to develop consensus guidelines on the use of cerebral embolic protection during TAVI based on the accumulated evidence.
Regulatory Considerations
The Sentinel device received FDA approval in 2017 based on the SENTINEL IDE trial, which showed the device could capture debris but missed its primary endpoint of reducing new brain lesion volume on MRI.
Dr. Giri emphasized that this outcome highlights a crucial lesson: "Surrogate endpoints are just not enough to guarantee clinical efficacy."
The BHF PROTECT-TAVI results underscore the importance of robust clinical trials in evaluating medical devices, particularly when intuitive mechanisms don't translate to measurable clinical benefits.
