Dr. Yusuf Bozkurt

Name of the Study: Randomized Invitation to Systematic NT-proBNP and ECG Screening in 75-Year Olds to Detect Atrial Fibrillation – STROKESTOP II

Published in Congress: ESC 2024

Link:  https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.071176

Background:
Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with increased morbidity and mortality, including a significantly higher risk of stroke and systemic embolism. Early detection and treatment of AF could mitigate these adverse clinical outcomes. Prior studies, such as STROKESTOP I, demonstrated that systematic AF screening could yield modest yet significant benefits in a population of 75-year-olds. Given that AF is often asymptomatic or paroxysmal, biomarkers like NT-proBNP (N-terminal pro-B-type natriuretic peptide) have been suggested to improve screening precision by identifying individuals at higher risk of AF, stroke, or embolism. STROKESTOP II aimed to build on these findings by investigating whether NT-proBNP-enhanced screening could reduce the incidence of stroke or systemic embolism in an elderly population.

Objective:
The primary aim of STROKESTOP II was to assess whether systematic screening for AF, enhanced by NT-proBNP measurements, would reduce the incidence of stroke or systemic embolism compared to a control group. A secondary aim was to determine if it was safe for individuals with low NT-proBNP concentrations (<125 ng/L) to forgo prolonged ECG monitoring without increasing their risk of stroke or embolism.

Methods:
This was a randomized, controlled trial conducted in the Stockholm Region, Sweden. All individuals aged 75 or 76 years were randomized 1:1 to either be invited to screening (intervention group) or serve as a control group receiving standard care. In the intervention group, participants underwent NT-proBNP testing. If their NT-proBNP level was ?125 ng/L, they were classified as high-risk and underwent extended ECG monitoring (four daily 30-second recordings for two weeks). Those with NT-proBNP levels <125 ng/L had only a single ECG recording and were classified as low-risk. The primary endpoint was the composite of stroke (ischemic or hemorrhagic) and systemic embolism. Data were obtained from the Swedish National Patient Register and Drug Register. Median follow-up was 5.1 years.

Results:
A total of 28,712 individuals were randomized, with 13,905 in the intervention group and 13,884 in the control group. After exclusions for death or emigration, 49.2% of those invited to screening participated. In the high-risk NT-proBNP group (?125 ng/L), which constituted 60% of the total intervention group, new AF was detected in 2.4% of participants (165 cases). At the end of follow-up, there was no statistically significant difference in the primary composite endpoint of stroke or systemic embolism between the intervention and control groups (HR: 0.96, 95% CI 0.86-1.06, p=0.412). However, in the low NT-proBNP group, the risk of stroke or systemic embolism was significantly lower than in the control group (HR: 0.59, 95% CI 0.46-0.74, p<0.001). Conversely, participants in the high NT-proBNP group had a higher risk of stroke or systemic embolism compared to those in the low NT-proBNP group (HR: 1.57, 95% CI 1.22-2.02, p=0.001).

Conclusion:
In this large, population-based randomized trial, systematic screening for AF using NT-proBNP as an enhancement biomarker did not significantly reduce the overall risk of stroke or systemic embolism compared to standard care. However, NT-proBNP effectively stratified individuals into risk groups, with low NT-proBNP levels identifying participants who could safely avoid prolonged screening. Despite the modest yield of newly diagnosed AF cases, the study demonstrated that NT-proBNP can be a valuable tool in identifying those at low risk for adverse outcomes.

Interpretations:
The STROKESTOP II trial highlights that while NT-proBNP is a useful biomarker for risk stratification, the overall effectiveness of systematic AF screening in preventing stroke or systemic embolism remains limited. The study was hindered by moderate participation rates, which may have diluted its ability to detect significant differences between groups. Furthermore, increasing awareness of AF over the years, coupled with higher baseline use of oral anticoagulation (OAC), likely reduced the potential impact of screening. Moving forward, efforts should focus on improving participation rates in screening programs and exploring additional biomarkers or technologies, such as artificial intelligence algorithms, to further enhance screening precision. Nonetheless, NT-proBNP proved valuable in reducing the need for prolonged ECG monitoring in low-risk individuals, highlighting its utility in optimizing screening protocols.