Apixaban Raises GI Bleeding Risk in Subclinical AF Compared to Aspirin: JAMA
Researchers have found in a new study that among patients with subclinical atrial fibrillation (SCAF), apixaban caused more major gastrointestinal bleeding than aspirin, though intracranial and fatal bleeding rates were similar. Most bleeding events were nonemergent, marked mainly by a drop in hemoglobin. The study was published in JAMA Cardiology by Deborah M. and colleagues.
The ARTESiA trial has previously shown that apixaban significantly reduces stroke and systemic embolism in patients with SCAF, while increasing major bleeding compared with aspirin. Subclinical atrial fibrillation, often detected by cardiac devices, is common in older adults and confers meaningful stroke risk. Because anticoagulation decisions depend heavily on the balance between thromboembolic risk and bleeding risk, detailed characterization of bleeding patterns is important. This prespecified subanalysis describes the nature, severity, and predictors of major bleeding in patients treated with either apixaban or aspirin to provide clinicians with deeper insight into risk stratification and safer prescribing practices.
This analysis utilized data from the international, double-blind ARTESiA randomized clinical trial. It evaluated 3961 patients with a SCAF episode of at least 6 minutes in duration to 24 hours, and stroke risk factors, defined as a CHA₂DS₂-VASc ≥3 or prior stroke. Participants were randomized to either apixaban 5 mg twice daily (or 2.5 mg twice daily when indicated) or aspirin 81 mg once daily. Major bleeding events were adjudicated by a blinded committee using International Society on Thrombosis and Hemostasis criteria. Data were analyzed from August to November 2024, with an average follow-up of 3.5 years.
Results
Among the 3961 patients (mean age 76.8 years, 64% male), 133 major bleeding events occurred:
86 events in the apixaban group (1989 patients)
47 events in the aspirin group (1972 patients)
This corresponded to:
1.71 versus 0.94 events per 100 patient-years
Hazard ratio (HR): 1.80 (95% CI, 1.26–2.57)
Intracranial bleeding:
0.33 vs 0.40 per 100 patient-years (HR 0.82; 95% CI, 0.43–1.57)
Fatal bleeding:
0.10% vs 0.16% per 100 patient-years (HR 0.63; 95% CI, 0.20–1.91)
Gastrointestinal bleeding:
0.89% vs 0.40% per 100 patient-years
HR 2.23 (95% CI, 1.32–3.78)
Notably, major bleeding events occurring in the apixaban group were less likely to occur at critical sites:
Critical-site bleeding: 27.9% vs 46.8% (P = 0.03)
Intracranial bleeding: 18.6% vs 42.6% (P = 0.003)
Most major bleeding events in both groups were nonemergent, defined mainly by a hemoglobin drop ≥2 g/dL.
Risk factors associated with major bleeding:
NSAID use: HR 10.25 (95% CI, 6.57–15.99)
Cancer: HR 2.87 (95% CI, 1.49–5.53)
Randomization to apixaban: HR 1.84 (95% CI, 1.29–2.63)
Increasing age: HR 1.47 (95% CI, 1.28–1.67 per 5 years)
This subanalysis of the ARTESiA trial shows that apixaban increases the risk of gastrointestinal bleeding but does not increase the risk of fatal or intracranial bleeding, with most bleeding events being nonemergent.
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