In the ARTESIA trial, how did apixaban compare with aspirin regarding the risk of stroke or systemic embolism?

Healey et al. conducted the ARTESIA trial, which assessed whether apixaban resulted in a lower risk of stroke or systemic embolism than aspirin, with an acceptably low risk of major bleeding, among patients with risk factors for stroke who also had subclinical atrial fibrillation detected by a pacemaker, defibrillator, or implantable cardiac monitor.

Clinical Pearls

Q: What is subclinical atrial fibrillation?

A: The authors proposed the term subclinical atrial fibrillation to describe atrial fibrillation that is asymptomatic or that produces such short-lasting, nonspecific symptoms that it is not readily diagnosed by standard clinical means but is uncovered only with the use of long-term, continuous cardiac rhythm monitoring by an implanted cardiac pacemaker or defibrillator. They reported that subclinical atrial fibrillation was present in more than one third of older patients with hypertension who had received a pacemaker and was associated with an increased risk of ischemic stroke or systemic embolism by a factor of 2.5. However, the absolute increase in stroke risk with subclinical atrial fibrillation was 1 percentage point per year, approximately half the risk increase observed among patients with clinically detected atrial fibrillation.

Q: In the ARTESIA trial, how did apixaban compare with aspirin regarding the risk of stroke or systemic embolism?

A: The trial showed that among patients with episodes of subclinical atrial fibrillation and risk factors for stroke, the risk of stroke or systemic embolism was lower by 37% (95% CI, 12 to 55) with apixaban than with aspirin. Stroke or systemic embolism (primary efficacy outcome) occurred in 55 patients assigned to receive apixaban (0.78% per patient-year) and 86 patients assigned to receive aspirin (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007).

Morning Report Questions

Q: Was the risk of bleeding higher with apixaban than with aspirin in the trial?

A: The risk of major bleeding was 1.71% per patient-year with apixaban and 0.94% per patient-year with aspirin (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Clinical presentation with hemodynamic instability was uncommon, and most bleeding events responded to supportive care, which could include red-cell transfusion. Fatal bleeding occurred in 5 patients with apixaban and 8 patients with aspirin. Symptomatic intracranial hemorrhage occurred in 12 patients with apixaban and 15 patients with aspirin.

Q: Are the trial findings generalizable to patients without an implanted cardiac electronic device?

A: Although the results of the ARTESIA trial are directly relevant to patients with implanted cardiac electronic devices, one might consider broader implications given the proliferation of implanted and wearable cardiac monitors as well as direct-to-consumer devices used to screen for atrial fibrillation. Although it was initially contemplated that the high prevalence of subclinical atrial fibrillation was confined to patients with pacemakers, subsequent studies involving implantable cardiac monitors showed subclinical atrial fibrillation in many older patients without pacemakers. Some of these patients may also have risk factors for stroke that are similar to those of the patients in the ARTESIA trial. However, the results of the ARTESIA trial apply directly only to patients who are already at increased risk for stroke in whom subclinical atrial fibrillation is detected by an implanted device.