Hemorrhage risk of direct oral anticoagulants in real-world venous thromboembolism patients.

Abstract Introduction Venous thromboembolism (VTE) management increasingly involves anticoagulation with direct oral anticoagulants (DOACs). Few studies have used competing-risks analyses to ascertain the mortality-adjusted hemorrhage and recurrent VTE (rVTE) risk of individual DOACs. Furthermore, hemorrhage risk factors in patients treated with apixaban remain underexplored. Materials and methods Patients diagnosed with VTE receiving anticoagulation were identified from the Optum Clinformatics Data Mart (2003–2019). Study endpoints included readmissions for intracranial hemorrhage (ICH), non-intracranial hemorrhage (non-ICH hemorrhage), and rVTE. Coarsened exact matching was used to balance baseline clinical characteristics. Complication incidence was evaluated using a competing-risks framework. We additionally modeled hemorrhage risk in apixaban-treated patients. Results Overall, 225,559 patients were included, of whom 34,201 received apixaban and 46,007 received rivaroxaban. Compared to rivaroxaban, apixaban was associated with decreased non-ICH hemorrhage (sHR = 0.560, 95%CI = 0.423–0.741), but not ICH, and rVTE (sHR = 0.802, 95%CI = 0.651–0.988) risk. This was primarily in emergent readmissions (sHR[emergent hemorrhage] = 0.515, 95%CI = 0.372–0.711; sHR[emergent rVTE] = 0.636, 95%CI = 0.488–0.830). Contributors to emergent hemorrhage in apixaban-treated patients include older age (sHR = 1.025, 95%CI = 1.011–1.039), female sex (sHR = 1.662, 95%CI = 1.252–2.207), prior prescription antiplatelet therapy (sHR = 1.591, 95%CI = 1.130–2.241), and complicated hypertension (sHR = 1.936, 95%CI = 1.134–3.307). Patients anticipated to be “high-risk” experienced elevated ICH (sHR = 3.396, 95%CI = 1.375–8.388) and non-ICH hemorrhage (sHR = 3.683, 95%CI = 2.957–4.588) incidence. Conclusions In patients with VTE receiving anticoagulation, apixaban was associated with reduced non-ICH hemorrhage and rVTE risk, compared to rivaroxaban. Risk reduction was restricted to emergent readmissions. We present a risk-stratification approach to predict hemorrhage in patients receiving apixaban, potentially guiding future clinical decision-making.