Systemic Embolic Events in Atrial Fibrillation

Study Questions:

What are the incidence, risk factors, and outcomes associated with extracranial systemic embolic events (SEEs) in nonvalvular atrial fibrillation (AF)?


Using four large contemporary randomized clinical trials of anticoagulation in AF (ACTIVE-A, ACTIVE-W, AVERROES, and RE-LY), incidence rates or SEEs were described. A total of 37,973 patients were included, with over 91,746 patient-years of follow-up. All suspected SEEs were independently re-adjudicated in a blind fashion. Included cases required new acute events located in the extracranial arterial vessels (e.g., new, acute limb ischemia). Objective evidence from imaging or surgical procedures was used to corroborate clinical evaluation.


SEE incidence rate was 0.24/100 patient-years compared with a stroke incidence rate of 1.92/100 patient-years. As compared with stroke, SEEs were more often seen in women (56% vs. 47%, p = 0.01), but had similar mean age (73.1 ± 8.5 vs. 73.5 ± 8.8 years, p > 0.3) and similar mean CHADS2 scores (2.41 ± 1.3 vs. 2.5 ± 1.2, p > 0.3). SEEs most frequently involved the lower extremities (58%), than visceral-mesenteric (31%) or upper extremity vessels (10%). SEE-related care involved hospitalization without a procedure in 30%, and endovascular or surgical intervention in 60% of cases. Full recovery within 30 days was reported in 54% of patients, while 24% of patients died. Thirty-day mortality was greater after a visceral-mesenteric embolism compared with lower or upper extremity SEEs (55% vs. 17% and 9%, respectively, p < 0.001 for both). The relative risk for death was 4.33 (95% confidence interval [CI], 3.29-5.70) after SSEs, and 6.79 (95% CI, 6.22-7.41) after stroke compared to patients without either event.


The authors concluded that SEEs consisted of 11.5% of clinically recognized thromboembolic events in AF patients.They also concluded that SEE-associated morbidity and mortality was high, comparable to that of ischemic stroke.


This study explores the often forgotten consequence of AF, namely extracranial thromboembolic events. While most patients (and practitioners) fear the consequences of AF-related stroke, extracranial SEEs are also prevalent and deadly. When patients present with systemic embolic phenomena, exploring for underlying AF is routine management. When discussing the consequences of AF and justification for anticoagulant therapy, clinicians should include SEEs alongside ischemic stroke.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Arrhythmias, Cardiac, Atrial Fibrillation, Anticoagulants, Embolism, Incidence, Peripheral Arterial Disease, Risk Factors, Secondary Prevention, Stroke, Thromboembolism

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