Biomarker Enhances Screening for Atrial Fibrillation

By Michael H. Crawford, MD, Editor

SYNOPSIS: A large Swedish population study of screening for atrial fibrillation (AF) in 75-year-old individuals that was enhanced by N-terminal pro-B-type natriuretic peptide (NT-proBNP) stratification did not identify more AF cases or prevent thromboembolic outcomes compared to unscreened control subjects. However, a low NT-proBNP (< 125 ng/L) did identify individuals at low risk for AF and thromboembolic events in whom screening could be safely forfeited.

SOURCE: Gudmundsdottir KK, Svennberg E, Friberg L, et al. Randomized invitation to systematic NT-proBNP and ECG screening in 75-year-olds to detect atrial fibrillation — STROKESTOP II. Circulation. 2024; Sep 1. doi: 10.1161/CIRCULATIONAHA.124.071176. [Online ahead of print].

Studies of clinical outcomes after electrocardiogram (ECG)-based atrial fibrillation (AF) screening have shown conflicting results. STROKESTOP-I (SS-I) showed a modest but significant benefit for a composite endpoint in subjects aged 75 years randomized to AF screening.¹ A subgroup with N-terminal pro-B-type natriuretic peptide (NT-proBNP; referred to in this article as pBNP) stratification showed enhanced performance with targeted screening. Thus, the primary aim of SS-II was to assess whether the selection of high-risk individuals based on pBNP, combined with more intense ECG monitoring, would reduce thromboembolic (TE) events in the intervention group compared to the control group receiving standard care.

The second aim was to assess the risk of TE in the low pBNP (< 125 ng/L) group, which did not have prolonged ECG screening, compared to the standard of care group. SS-II is a parallel group, unmasked, randomized controlled trial with unblinded registry-based outcomes. Patient data were collected from the Swedish National Patient Register and Drug Register. All residents of the Stockholm region born between 1940 and 1941 were eligible for the study and divided 1:1 into a control group or an intervention group by Statistics Sweden based on sex and age.

The control group received no information about the study. The intervention group was invited to a screening visit, where a medical history, height, and weight were obtained. If they had a previous history of AF or they were in AF at the visit,or had a pBNP > 900 ng/L, they were excluded. Those who gave informed consent were the intervention group. They were divided into those with a pBNP ≥ 125 ng/L (the high-risk group) and those with a pBNP < 125 ng/L (the low-risk group).

Those in the high-risk group underwent a two-week long recording of a single-lead ECG four times daily for 30 seconds. The first primary outcome was stroke and systemic thromboembolism (STE) in the intervention group vs. the control group. The second primary outcome was STE in the low-risk group compared to the control group. Secondary outcomes included hemorrhagic stroke, death, dementia, and pulmonary embolism.

A total of 28,712 individuals were randomized (13,905 in the intervention group and 13,884 in the control group) between 2016 and 2018. In the intention-to-screen group, 6,843 subjects (49%) accepted the invitation. Their mean age was 76.5 years, 53% were women, and their average CHA₂DS₂-VASc score was 3.5. New AF was detected in 2.4% of the intervention group, and 95% were started on an oral anticoagulant.

After a five-year mean follow-up, there was no difference in the prevalence of anticoagulation treatment or in the incidence of STE events between the intervention and control groups. The low pBNP group had fewer STE events than the control group (hazard ration [HR], 0.59; 95% confidence interval [CI], 0.46-0.74; P < 0.001) and the high pBNP group had more STE events than the low group (HR, 1.57; 95% CI, 1.22-2.02; P = 0.001). None of the secondary outcomes were significantly different.

The authors concluded that in this population-based trial to screen for AF, there was no difference in the risk of STE between the intervention group and the control group, and the use of pBNP identified a low-risk group who could safely forgo screening for AF.

Commentary

The novel aspect of SS-II was the use of pBNP to stratify patients into high- and low-risk groups to facilitate targeted AF screening. Although pBNP stratification did identify a high- and low-risk group for subsequent STE, there was no difference in AF cases identified and, unlike SS-I, there was no evidence that STE events were prevented compared to the control group. One caveat is that the very low incidence of AF detected by screening (2.4%) resulted in a low positive predictive value.

One reason for the low incidence of AF may be that the 49% who agreed to the screening visit had a higher socioeconomic status, fewer comorbidities, and lower CHA₂DS₂-VASc scores than those who declined participation. Given the low risk of detecting AF or subsequent STE events in those with a low pBNP, prolonged screening for AF could safely be forfeited.

There are limitations to SS-II. The prolonged screening protocol required a great deal of cooperation from the subjects. A two-week continuous patch monitor would be more convenient and would provide more data. Selecting subjects who are about 75 years of age enhances the likelihood of detecting AF but limits generalizability, as does the racially homogeneous population.

The participation rate was low, and few cases of AF were detected. Although oral anticoagulant use was high in those with AF (82% at the end of the trial), there was no information on other treatments, such as ablation or left atrial appendage ligation.

SS-II, while not particularly informative, does add to the growing knowledge base on screening for AF and supports the notion that future trials should focus on higher-risk individuals beyond just older adults.

REFERENCE

1. Svennberg E, Friberg L, Frykman V, et al. Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP): A multicentre, parallel group, unmasked, randomised controlled trial. Lancet. 2021;398(10310):1498-1506.

Michael H. Crawford, MD, is a Professor of Medicine and Consulting Cardiologist, University of California Health, San Francisco.