Anticoagulant Benefit in Subclinical Atrial Fibrillation Accounting for Competing Risks: A Reanalysis of the ARTESIA Trial.

Abstract

Background: The ARTESIA trial showed apixaban reduced the relative hazard of stroke/systemic embolism in subclinical atrial fibrillation (SCAF; 6 min-24 hr) by 37%, but did not report absolute risk reduction (ARR). The reported Kaplan-Meier analysis and incidence rate reduction did not account for the competing risk of death or 24-hour AF events. We reanalyzed ARTESIA accounting for competing risks to determine the ARR of apixaban vs. aspirin.

Methods: Individual time-to-event and time-to-censoring data were extracted from the published Kaplan-Meier curve. ARTESIA classified deaths and 24-hour AF events as censoring events. We probabilistically reclassified them to competing events to estimate the ARR accurately. We used the Aalen-Johansen estimator to estimate the cumulative risk of stroke/systemic embolism, accounting for competing events.

Results: After reclassification of deaths and 24-hour AF to competing events, there were 1111 censoring and 852 competing events in the apixaban arm, and 1100 censoring and 816 competing events in the aspirin arm. At 6 years, the ARR was 2.09% (95% CI -0.17 to 4.34) when death and 24-hour AF events were treated as censoring events vs. 1.68% (95% CI 0.46 to 2.89) when they were treated as competing events.

Conclusion: In SCAF, apixaban reduced the 6-year risk of stroke/systemic embolism by 1.68%, a 20% lower benefit when accounting for competing risks. Accounting for competing risks is essential to accurately measure the benefit of anticoagulants for SCAF.