A Precision Pulse: Navigating Subclinical Atrial Fibrillation with Apixaban

Ameer El-Afandi, PharmD, 1st year PCLR resident - M Health Fairview Smiley’s Clinic

Background: Subclinical atrial fibrillation (AF) is a subtype of AF that is asymptomatic and is short in duration. Subclinical AF can usually be identified through continuous monitoring with pacemakers or defibrillators, and has also been associated with increased risk of stroke by 2.5 fold, but it is unclear how treatment with oral anticoagulation benefits patients diagnosed with subclinical AF.

Objective: To assess the clinical benefit and safety of using oral anticoagulation in patients with subclinical AF.

Study Design: The study was a randomized double-blind, double dummy trial designed to place patients either on apixaban 5 mg twice a day (or 2.5 mg twice a day when indicated) or aspirin 81 mg once a day. The study included 4012 patients, 2015 in apixaban and 1997 in aspirin groups, with subclinical AF who were 76.8 +7.6 years and had a mean CHA2DS2-VASC score of 3.9+1.1. The trial was conducted in 16 European and North American countries. Eligible patients had subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor with one episode lasting >6 minutes but not longer than 24 hours. Patients were also required to have a CHA2DS2-VASc score of >3. The minimum age required for patients was 55 years. The primary efficacy outcome was the composite of stroke and systemic embolism  assessed in the intention-to-treat population. The primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Haemostasis. Additional outcomes included the cause-specific mortality, stroke subtype, and transient ischemic attack with aphasia, motor deficit, or a duration of >5 minutes.

Results: Stroke or systemic embolism occurred in 55 patients assigned to apixaban (55/2015) and 86 patients assigned to aspirin (86/1997 (HR: 0.63, CI: 0.45-0.88, P=0.007). The risk of disabling or fatal stroke was reduced by 49% in the apixaban group as compared to the aspirin group (HR: 0.51, CI: 0.29-0.88). The rate of disabling or fatal stroke in the respective groups was 33% vs 48%. The risk of major bleeding was 1.71% per patient year with apixaban vs 0.94% per patient year with aspirin (HR: 1.80, CI: 1.26-2.57, P=0.001).

Conclusion: Among patients with subclinical AF, apixaban has a lower risk of stroke or systemic embolism but has a higher rate of major bleed when compared to aspirin.

Key points: When considering the clinical effects of apixaban in patients with subclinical AF, the risks and benefits must be assessed. Fewer cases of stroke have been reported in patients with subclinical AF on apixaban when compared to aspirin; however, more cases of major bleeding events were reported with apixaban. Some limitations of the study include not comparing other direct oral anticoagulants like rivaroxaban, and the study only included patients with implanted devices. The effect of apixaban lowering the risk of stroke or systemic embolism included a significant group difference in disabling or fatal stroke. This study can impact future practice by reducing stroke risk in patients with identified subclinical atrial fibrillation.


Healey JS, Lopes RD, Granger CB, et al. Apixaban for stroke prevention in subclinical atrial fibrillation. N Engl J Med. 2024;390(2):107-117 DOI: 10.1056/NEJMoa2310234