Dr. Yusuf Bozkurt Şahin

Name of the Study: Comparative Analysis of Cerebral Embolic Protection by Geographic Region: Insights from the PROTECTED TAVR Trial

Published in Congress: TCT 2024

Link:  https://jamanetwork.com/journals/jamacardiology/fullarticle/2825480

Background:

Transcatheter aortic valve replacement (TAVR) has emerged as a standard intervention for severe symptomatic aortic stenosis, even among low-risk surgical candidates. Despite its benefits, TAVR carries a risk of embolic stroke due to dislodged debris during valve placement. The Sentinel cerebral embolic protection (CEP) device was developed to mitigate this risk by capturing embolic particles during TAVR procedures. However, previous studies on CEP efficacy have shown mixed results, particularly due to the variability in clinical outcomes. The PROTECTED TAVR trial, the largest of its kind, aimed to evaluate CEP's impact on stroke outcomes across different regions, providing an opportunity to examine regional differences in patient characteristics and procedural practices that may influence outcomes.

Objective:
To investigate the efficacy of routine CEP use in reducing periprocedural stroke risk during TAVR and assess whether stroke reduction differs between patients in the United States (US) and those outside the United States (OUS).

Methods:
The PROTECTED TAVR trial was a prospective, multicenter, randomized trial conducted from February 2020 to January 2022 across 51 centers in the US, Europe, and Australia. Patients with symptomatic aortic stenosis undergoing transfemoral TAVR were randomly assigned in a 1:1 ratio to receive TAVR with or without the Sentinel CEP device. Stratification included center, operative risk, and intended valve type. Exclusions were made for patients with significant stenosis (>70%) in the left common carotid or brachiocephalic arteries or if vascular anatomy was incompatible with the device. Primary outcomes included the incidence of stroke within 72 hours post-procedure or upon discharge. Stroke severity, disabling versus non-disabling, was adjudicated based on the modified Rankin Scale, and neurological assessments were conducted pre- and post-procedure.

Results:
The trial enrolled 3,000 patients (mean age: 78.9 years; 60.1% male), with 1,833 participants in the US cohort (914 with CEP, 919 without) and 1,167 participants in the OUS cohort (587 with CEP, 580 without). US patients were younger, more likely to be male, and had higher rates of bicuspid aortic valve disease, diabetes, and peripheral vascular disease compared to OUS patients. The main analysis revealed that CEP did not significantly lower the primary endpoint of all strokes, with rates of 2.3% in the CEP group and 2.9% in the control group (p=0.30). However, CEP was associated with a significant reduction in disabling strokes within the US cohort, showing a 50% relative risk reduction (1.3% with CEP vs. 2.6% without; p=0.045) and a 73% relative reduction in disabling stroke (0.4% vs. 1.5%; p=0.02). Conversely, OUS participants did not show significant benefit from CEP (3.7% with CEP vs. 3.3% without; p=0.66).

Conclusion:
The PROTECTED TAVR trial’s findings indicate that while CEP use did not significantly reduce overall stroke incidence in the full cohort, there was a notable trend toward stroke reduction in the US cohort that was not observed in the OUS group. This variation may reflect underlying regional differences in patient characteristics and procedural approaches. These exploratory results highlight the need for further research to clarify the factors influencing CEP efficacy and determine if specific patient subgroups, particularly within the US, may derive more benefit from CEP.

Interpretations:
This post hoc analysis highlights possible regional differences in the effectiveness of CEP, indicating that variations in patient characteristics and procedural methods could influence device performance. While the trial did not demonstrate a statistically significant impact of CEP in reducing overall stroke rates, the observed trend in the US cohort points to the need for further study. These findings may shape clinical guidelines, advocating for CEP use in specifically chosen patient groups, especially in regions with similar patient demographics to those in the US.