Patients with cancer are at higher risk of developing venous thromboembolism (VTE) compared with the general population. This elevated risk is due to several risk factors and multiple, overlapping thrombotic and hemostatic pathophysiological pathways that are specific to this patient population. Hence, the management of cancer-associated VTE can be challenging for clinicians. Patients with cancer-associated VTE are at higher risk of both recurrent events despite anticoagulation and bleeding complications due to the anticoagulant regimens. Direct oral anticoagulants have recently been shown to be effective, safe, and more convenient than parenteral low-molecular-weight heparin for the management of cancer-associated VTE. Despite these recent advances in anticoagulant therapy, many unmet needs remain in these patients (increased risk of bleeding with specific cancer types, drug-to-drug interactions, liver dysfunction). Factor XI inhibitors are currently being assessed for the management of cancer-associated VTE and may help clinicians address these important knowledge gaps.

Introduction: Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular comorbidities may take both antiplatelet and oral anticoagulation therapy (OAC/AP). Our study aims to evaluate the safety and efficacy of OAC/AP therapy as secondary prevention in people with AF and ischaemic stroke. Patients and methods: We performed a post-hoc analysis of pooled individual data from multicenter prospective cohort studies and compared outcomes in the OAC/AP cohort and patients on DOAC/VKA anticoagulation alone (OAC cohort). Primary outcome was a composite of ischaemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding, while secondary outcomes were ischaemic and haemorrhagic events considered separately. A multivariable logistic regression analysis was performed to identify independent predictors for outcome events. To compare the risk of outcome events between the two cohorts, the relation between the survival function and the set of explanatory variables were calculated by Cox proportional hazard models and the results were reported as adjusted hazard ratios (HR). Finally another analysis was performed to compare the overall risk of outcome events in both OAC/AP and OAC cohorts after propensity score matching (PSM). Results: During a mean follow-up time of 7.5 ± 9.1 months (median follow-up time 3.5 months, interquartile range ±3), 2284 stroke patients were on oral anticoagulants and 215 were on combined therapy. The multivariable model demonstrated that the composite outcome is associated with age (OR: 1.03, 95% CI: 1.01–1.04 for each year increase) and concomitant antiplatelet therapy (OR: 2.2, 95% CI: 1.48–3.27), the ischaemic outcome with congestive heart failure (OR: 1.55, 95% CI: 1.02–2.36) and concomitant antiplatelet therapy (OR: 1.93, 95% CI: 1.19–3.13) and the haemorrhagic outcome with age (OR: 1.03, 95% CI: 1.01–1.06 for each year increase), alcoholism (OR: 2.15, 95% CI: 1.06–4.39) and concomitant antiplatelet therapy (OR: 2.22, 95% CI: 1.23–4.02). Cox regression demonstrated a higher rate of the composite outcome (hazard ratio of 1.93 [95% CI, 1.35–2.76]), ischaemic events (HR: 2.05 [95% CI: 1.45–2.87]) and bleeding outcomes (HR: 1.90 [95% CI, 1.06–3.40]) in OAC/AP cohort. After PSM analysis, the composite outcome remained more frequent in people treated with OAC + AP (RR: 1.70 [95% CI, 1.05–2.74]). Discussion: Secondary prevention with combination of oral anticoagulant and antiplatelet therapy after ischaemic stroke was associated with worse outcomes in our cohort. Conclusion: Further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischaemic stroke in patients with atrial fibrillation.