Abstract TP148: Long term efficacy and safety of combined antiplatelet/anticoagulant therapy vs monotherapy in patients with atrial fibrillation after a stroke; RAFFINE and SAKURA registries sub analysis

Background: Atrial fibrillation (AF) is a major risk factor for stroke, requiring anticoagulation therapy for secondary prevention. However, in cases with coexisting atherosclerosis, antiplatelet therapy is sometimes added, despite concerns about increased bleeding risk. This study evaluated the long-term efficacy and safety of combination therapy in patients with AF and prior stroke. Methods: We conducted a post hoc analysis of two large-scale prospective registries, RAFFINE and SAKURA, including 922 AF patients with prior stroke receiving anticoagulation therapy. Patients were divided into those receiving anticoagulation alone and those receiving anticoagulation plus antiplatelet therapy. Clinical outcomes were assessed over five years using Kaplan-Meier analysis and Cox proportional hazards models. Results: Of 922 patients, combination therapy with antiplatelets were older, more often female, and had higher prevalence of hypertension, diabetes, dyslipidemia, ischemic heart disease, peripheral artery disease, and renal dysfunction. In Kaplan-Meier analysis, the combination therapy group showed a trend toward higher cardiovascular events and all-cause mortality compared to monotherapy (p=0.052 and 0.083, respectively), especially in the DOAC group (p=0.041 and 0.012). Cox proportional hazard analysis revealed no significant association between combination therapy and any efficacy outcomes. Safety analysis showed a trend toward increased intracranial bleeding in the combination group (p = 0.082), particularly with DOACs (p=0.096), though not statistically significant in Cox analysis. In sub-analysis by AF type, combination therapy significantly increased cardiovascular events in persistent/permanent AF (p=0.027), but not in paroxysmal AF. Cox analysis confirmed no efficacy differences by AF type. Notably, in persistent AF, combination therapy was associated with significantly increased intracerebral hemorrhage (HR 3.860, 95%CI 1.248–11.933, p=0.019). Across analyses, older age, CHF, and renal dysfunction were commonly associated with adverse outcomes. Conclusion: The addition of antiplatelet therapy to anticoagulation in patients with AF and prior stroke did not confer clinical benefit and was associated with increased risks of ischemic events and mortality, especially among DOAC users. Careful management of underlying conditions—including heart failure, dyslipidemia, and renal dysfunction—is essential for optimizing outcomes in this patient population.