Apixaban Reduces Risk for Covert Infarcts in Patients With Atrial Cardiopathy

Among patients with cryptogenic stroke and atrial cardiopathy, treatment with apixaban results in a lower incidence of nonlacunar covert infarcts compared to aspirin, according to study results published in JAMA Neurology. These findings suggest that apixaban may provide additional protection against silent cerebrovascular injury, which has been linked to cognitive decline and increased stroke risk.

Covert brain infarcts, which occur without overt stroke symptoms, are common in patients with vascular risk factors and atrial dysfunction. While the primary ARCADIA trial (ClinicalTrials.gov Identifier: NCT03192215) found no significant difference in recurrent stroke rates between apixaban and aspirin in this population, the effect of anticoagulation on covert infarcts remained unclear. To evaluate this, researchers conducted a secondary analysis using MRI data from a subset of ARCADIA participants.

Investigators carried out the multicenter, randomized, double-blind ARCADIA trial, enrolling patients from 75 sites across the US between November 2019 and December 2022. Participants in the primary ARCADIA trial were invited to coenroll in ARCADIA-MRI if they had not permanently discontinued their study medication and had no contraindications to magnetic resonance imaging (MRI). Out of the 799 participants in the parent trial, 310 (31%) enrolled in the ARCADIA-MRI study. Of those, 174 participants (56%) had both baseline and follow-up MRI scans available for analysis.

The primary outcome was the incidence of new nonlacunar covert infarcts, assessed by 2 independent, blinded raters. Nonlacunar covert infarcts were defined as ischemic brain lesions distinct from lacunar infarcts (small subcortical lesions <15 mm) and not attributable to baseline infarcts.

The baseline characteristics were evenly distributed between the apixaban group (n=79) and the aspirin group (n=95). Participants had a mean age of 66 years, with 52.3% identified as men. The median follow-up time to MRI was 27 (16 to 43) months in both groups. Cohen κ for interrater agreement on detecting covert infarcts was 80.9% for any infarct, 80.4% for lacunar infarcts, and 81.4% for nonlacunar infarcts.

During follow-up, new nonlacunar covert infarcts occurred in 5.1% (n=4/79; annualized rate 2%) of the apixaban group versus 17.9% (n=17/95; annualized rate 7.4%) of the aspirin group. This represented a weighted relative risk (RR) of 0.29 (95% CI, 0.10-0.83; P =.02). Apixaban also lowered the risk for the secondary composite endpoint (weighted RR, 0.36; 95% CI, 0.17-0.79; P =.01).

The findings were consistent across unweighted analyses, with no subgroups showing a distinct treatment effect for either primary or secondary outcomes. Additionally, no significant difference in risk reduction was observed between covert lacunar and nonlacunar infarcts (Wald z statistic: -1.35; P =.18).

Study limitations include a small sample size, potential selection bias from participants likely to adhere to treatment, and potential MRI infarct detection issues.

“…the ARCADIA-MRI results suggest that apixaban compared to aspirin was associated with fewer incidents nonlacunar covert infarcts among patients with cryptogenic stroke and atrial cardiopathy,” the researchers concluded.

This research was supported by the National Institute of Neurological Disorders and Stroke. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on The Cardiology Advisor