The ARTESIA trial - Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation

Presented at the AHA Scientific Sessions 2023 by: Jeff Healey, MD- Hamilton, ON, Canada

Introduction and methods

Background

Subclinical atrial fibrillation refers to brief episodes of atrial fibrillation which are asymptomatic and detected only with long term continuous monitoring, such as a pacemaker or implanted defibrillator. Patients with subclinical atrial fibrillation have a 2.5-fold increased risk of stroke. This risk appears to be lower than in patients with clinical atrial fibrillation (which is 4 to 5-fold). Therefore, the value of oral anticoagulation in patients with subclinical atrial fibrillation has been questioned.

Aim of the study

The ARTESIA study aimed to investigate the value of apixaban compared with aspirin in patients with subclinical atrial fibrillation.

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Methods

ARTESIA was a randomized double blind study conducted at 247 centers in 16 countries. The study enrolled patients with an implanted pacemaker, defibrillator or cardiac monitor who had subclinical atrial fibrillation lasting between 6 minutes and 24 hours. Eligible patients were aged ≥ 55 years with a CHA2DS2-VASc score of ≥3, or they could have a history of stroke or aged ≥ 75 years. A total of 4012 patients were randomized in a 1:1 ratio to receive apixaban (5 mg BID or 2.5 mg BID according to label) or aspirin (81 mg/day). Mean follow up was 3.5 ± 1.8 years.

Outcomes

The primary endpoint was stroke or systemic embolism. The safety endpoint was major bleeding. The primary endpoint was analyzed in the intention to treat population, whereas the bleeding outcome was assessed in an on-treatment analysis to provide greater sensitivity.

Main results

• Apixaban reduced the primary outcome of stroke or systemic embolism by 37%, compared with aspirin (HR 0.63, 95%CI 0.45-0.88, P=0.007).
• Apixaban reduced total stroke (HR 0.64, 95%CI 0.46-0.90) and ischemic stroke (HR 0.62, 95%CI 0.43-0.91). There was no difference between groups for hemorrhagic stroke (HR 0.76, 95%CI 0.33-1.73) and CV death (HR 0.96, 95%CI 0.73-1.25).
• Moderately to severe disabling strokes (Mod. Rankin Score 3-6) were reduced by 49% in the apixaban arm compared with the aspirin arm (HR 0.51, 95%CI 0.29-0.88).
• There was an increased risk of major bleeding in the apixaban arm, compared with the aspirin arm (HR 1.80, 95%CI 1.26-2.57, P=0.001). There was no statistical difference between groups for fatal bleeding (HR 0.63, 95%CI 0.20-1.91), symptomatic intracranial hemorrhage (HR 0.77, 95%CI 0.36-1.64), or transfusion-requiring bleeding (HR 1.43, 95%CI 0.78-2.61).
• The risk benefit analysis on the intention to treat population showed that there were 4.6 fewer strokes or emboli with 4.1 more major bleeds with apixaban compared with aspirin. To place these number into context, Jeff Healey pointed out that among the strokes in the trial, 45% of the strokes in aspirin treated patients were permanently disabling or fatal, these strokes were reduced by 49% with apixaban. 20% of major bleeds on apixaban were related to hemodynamic instability or neurological symptoms, and there was no increase in fatal or intracranial bleeding with apixaban.

Conclusion

The ARTESIA trial showed that apixaban reduced stroke or systemic embolism in patients with subclinical atrial fibrillation compared with aspirin. Apixaban increased the risk of major bleeding but there was no increase in intracranial bleeding or fatal bleeding.

Jeff Healey said: “We feel that anticoagulation should be at least considered among patients with subclinical atrial fibrillation who have additional stroke risk factors.”

- Our reporting is based on the information provided at the AHA Scientific Session 2023-

The results of this study were simultaneously published in N. Engl. J. Med.