Use of apixaban in patients with sub-clinical atrial fibrillation (AF) resulted in a lower risk of stroke or systemic embolism than aspirin, but a higher risk of major bleeding, results of the ARTESIA randomised trial, presented at the American Heart Association’s 2023 Scientific Sessions (11–13 November, Philadelphia, USA) have shown.
Sub-clinical AF is brief, asymptomatic AF that is detected by pacemakers, implantable defibrillators and cardiac monitors. Previous research has indicated that treatment with oral anticoagulants may prevent up to two-thirds of strokes in people diagnosed with AF, but may cause an increased risk of major bleeding, including blood in stool or in urine, and/or trauma-related bleeding.
“We have observed in previous research that the magnitude of stroke risk associated with short duration, asymptomatic, subclinical atrial fibrillation was lower than what was seen in people with longer-lasting symptomatic atrial fibrillation,” said study author Jeff Healey (McMaster University, Hamilton, Canada). “So that is a different risk-benefit consideration for prescribing anticoagulants.”
This phase 4 clinical trial examined the risk-benefit considerations of treating asymptomatic AF. Researchers enrolled 4,012 adults from 16 countries in North America and Europe who had an implanted pacemaker, defibrillator or cardiac monitor that detected asymptomatic atrial fibrillation.
Half of the participants were randomly assigned to receive 5mg of apixaban twice daily, or 2.5 mg twice daily in patients meeting a pre-set criteria for dose reduction such as being over age 80 or weighing less than 132 pounds. The other half of the participants received 81mg of aspirin daily. Neither participants nor researchers knew which medication participants were taking. Researchers monitored study participants for an average of 3.5 years for stroke, blood clots and/or major bleeding.
Investigators reported that those in the apixaban group had a 37% overall reduction in incidence of stroke or blood clots, driven mainly by a 51% reduction in fatal or disabling strokes, but, among patients actively taking study medication, the risk of major bleeding was 74% higher in the apixaban group compared to the aspirin group (1.69% per year vs. 0.96% per year).
Nominally fewer major bleeds in the apixaban arm presented with neurological symptoms or critically low blood pressure (18.5% vs. 26%) or were fatal at presentation (1.1% vs. 4%). Fewer than 10% of the bleeds required life-saving intervention such as surgery (9.8% in the apixaban group and 8% in the aspirin group).
There were no differences noted for the most severe bleeds between the aspirin-treated participants and the apixaban-treated participants, such as fatal bleeds, bleeds requiring surgery or bleeds requiring blood transfusion.
In this trial, the rate of major bleeds was 1.69% per year in the apixaban group, which is similar or lower than anticipated, based on earlier major studies of these medications to treat Fib, according to Healey.
“Currently, there is no consistent guidance on how to treat subclinical atrial fibrillation in people with implanted heart devices. I think the results of ARTESIA are strong enough to change the way we practice and lead to changes in management guidelines so that we recommend that many of these individuals who have subclinical AF receive an anticoagulant,” said Healy. “The study’s findings will also help to address ongoing questions about the potential value of population-based screening for AF.”