Apixaban Reduces the Risk of Hemorrhage in VTE Patients

In assessing hemorrhage risk factors for venous thromboembolism (VTE) patients taking direct oral anticoagulants (DOACs), the use of apixaban is correlated with reduced non-intracranial hemorrhage (ICH) and recurrent (rVTE) risk, compared to rivaroxaban, according to a study published in Thrombosis Research. Traditionally, VTE has been treated orally using vitamin K antagonists, such as warfarin. More recently, DOACs have been administered instead due to convenience, lack of monitoring requirements, and mounting evidence of fewer bleeding events associated with DOACs compared to warfarin. Previous studies have showed that using DOACs, such as apixaban, is actually safer than warfarin with respect to the risk of brain hemorrhage in patients with DVT/PE without atrial fibrillation. Researchers of this study sought to comprehensively assess hemorrhage risk and rVTE in patients taking DOACs to treat VTE. This study comprised 225,559 patients with VTE; of whom 34,201 received apixaban and 46,007 received rivaroxaban. Patients were identified using the Optum Clinformatics Data Mart (2003–2019). The study endpoints were defined as readmissions for intracranial hemorrhage (ICH), non-intracranial hemorrhage (non-ICH hemorrhage), and rVTE.
According to the results of the study, compared to rivaroxaban, apixaban was associated with both a decreased risk of 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), the researchers noted.
The study identified several contributors to emergent hemorrhage in apixaban-treated patients; including 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).
In terms of limitations, the research team noted the standard limitations associated with retrospective data-driven investigations; including potential selection bias, missing variables, and miscoded or missing data. Moreover, all diagnoses and prescriptions they analyzed were identified based on standardized coding systems, and clinical notes are not available to verify billed claims.
“Apixaban was associated with lower overall risk of hemorrhage and readmission for rVTE compared to rivaroxaban when treating patients with VTE without atrial fibrillation, even when excluding events taking place during a fixed three-week loading phase. These differences were derived after adjusting for outpatient mortality as a competing risk and translated into reductions in the number of emergency readmissions. Complicated hypertension and pulmonary disease, among other risk factors, were major contributors to hemorrhage risk on apixaban. In a risk-stratification exercise predicting hemorrhage risk at start of apixaban, we identified a subset of patients with a three-fold increase in bleeding risk who may benefit from closer monitoring and more frequent assessment of the risks and benefits of anticoagulation,” the researchers concluded.