Risk of recurrent stroke in patients with atrial fibrillation treated with oral anticoagulants alone or in combination with anti-platelet therapy

Abstract

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.

The Impact of Atherosclerotic Burden on Vascular Outcomes in Patients with Stroke and Atrial Fibrillation: The ATHENA study

“… 24 Adherence to such an approach has been associated with improved clinical outcomes, including a lower relative risk of death, stroke, bleeding, and hospitalization. 23 , 24 In our study, patients with AVD were taking less oral anticoagulant therapy and more statins on admission, consistent with a prior study. 25 Despite these patients having higher cardiovascular risk, they tended to be undertreated and to have more severe strokes at admission.…”

“…However, add-on treatment with aspirin does not reduce the recurrence risk but increases only the hemorrhagic risk. 23 A possible strategy in these patients would be an optimal control of vascular risk factors, which is part of the current holistic or integrated care approach to AF management recommended in guidelines. 24 Adherence to such an approach has been associated with improved clinical outcomes, including a lower relative risk of death, stroke, bleeding, and hospitalization.…”

Impact of left ventricular diastolic function and direct oral anticoagulant use for predicting embolic events in patients with heart failure and atrial fibrillation

“…Although there is controversy regarding the efficacy and safety of combined anticoagulant and antiplatelet therapy in this patient population, in a cohort study of patients with AF, combination therapy was associated with an increased risk of major bleeding and stroke, regardless of whether atherosclerotic disease was present. 38 Similar results were reported for patients with AF and a history of ischemic stroke, 39 and there is currently much negative evidence regarding combination therapy.…”