The baseline CHA₂DS₂-VASc score helped to identify patient with subclinical atrial fibrillation (SCAF) in whom the benefit for reducing the risk of stroke and systemic embolism (SE) with an oral anticoagulant (OAC) was greater than the risk of increased major bleeding, according to a subgroup analysis from the ARTESiA study presented at Heart Rhythm 2024 and simultaneously published in JACC.

The randomized ARTESiA study showed that apixaban, compared with aspirin, significantly reduced stroke and SE but at the cost of increased major bleeding in patients with SCAF, who were at least 55 years old and had a CHA₂DS₂-VASc of ≥3. SCAF had been detected by an implanted pacemaker, defibrillator or cardiac monitor, with at least one episode of ≥six minutes but no episodes >24 hours. Patients either received five mg of apixaban daily (eventually reduced to 2.5 mg per guidelines) or 81 mg of aspirin daily.

In this subanalysis, conducted by Renato D. Lopes, MD, PhD, FACC, et al., the mean age of the patients was 76.8 years and 36.1% were women. Baseline CHA₂DS₂-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%) and >4 in 1,085 (27.0%).

Results showed that the annual stroke rate for patients with a CHA₂DS₂-VASc score >4 was 0.98% with apixaban and 2.25% with aspirin (hazard ratio [HR], 0.44), with apixaban preventing 1.28 strokes/SE per 100 patient-years and causing 0.68 major bleeds.

With apixaban vs. aspirin in patients with a CHA₂DS₂-VASc score <4, the annual stroke/SE rate was 0.85% and 0.97% (HR, 0.87), with apixaban preventing 0.12 strokes/SE per 100 patient-years and causing 0.33 major bleeds. For patients with CHA₂DS₂-VASc score of 4, the annual rate of stroke/SE was 0.54 and 0.86, respectively (HR, 0.63), with apixaban preventing 0.32 strokes/SE per 100 patient-years and causing 0.28 major bleeds.

“One in four patients in ARTESiA with SCAF had a CHA₂DS₂-VASc score >4 and a stroke/SE risk of 2.2% per year,” write the authors. “These patients should generally be treated with an OAC, as it appears to prevent nearly twice as many strokes/SE compared with the major bleeds that it causes.” The authors write that the opposite is true for patients with CHA₂DS₂-VASc score <4, and that there is a substantial intermediate group (CHA₂DS₂-VASc 4) in which patient preferences will inform treatment decisions.

In an accompanying editorial comment, Sachin J. Shah, MD, MPH, writes that “the study authors meaningfully advance our understanding of who to treat – those with a CHA₂DS₂-VASc score of 5 or more appear to have a greater net benefit from anticoagulants. Nevertheless, important open questions remain, including how to incorporate prior stroke history and AFib burden into anticoagulant treatment recommendations for people with SCAF. For some physicians, these data alone may be sufficient to initiate treatment for patients whose values and preferences align with treatment. However, for many, the treatment paradigm is not yet settled.”