Risk of death, thrombotic and hemorrhagic events in patients with atrial fibrillation and systemic autoimmune diseases

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Abstract Background Growing evidence showing that systemic autoimmune diseases (SAD) are associated with a high risk of incident atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. Purpose To assess the risk of all-cause death, thrombotic events, and bleeding in AF patients with SAD. Methods Retrospective cohort study within a global health care network (TriNetx). Using ICD codes, AF patients were categorized into two groups: 1) AF patients with SAD (M32: Systemic Lupus Erythematosus; M33: Dermato-polymyositis; M34: Systemic Sclerosis; M35: Sjogren syndrome), and 2) AF controls (without systemic autoimmune, autoinflammatory, or rheumatic diseases). The primary outcomes were the 5-year risks of 1) all-cause death, 2) thrombotic events (ischemic stroke, transient ischemic attack, peripheral arterial thromboembolism, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and 3) hemorrhagic outcome (intracranial hemorrhage and gastrointestinal bleeding). Secondary outcomes were each component of the composite primary outcomes. Cox regression analysis before and after propensity-score-matching (PSM) was used to estimate HR and 95% confidence interval (95%CI). Sensitivity analyses were done to investigate the risk of primary outcomes associated with each systemic autoimmune disease and with different types of oral anticoagulant (OAC). Results We identified 22,371 AF patients with SAD (67.7±13.7 years, 72.2% females), and 1,478,693 AF controls (69.7±14.0, 42.6% females). Before PSM, AF patients with SAD were younger, more often females, and with a higher prevalence of cardiovascular risk factors; no differences were found after PSM. After PSM, AF patients with SAD showed a higher risk of all-cause death (HR 1.21, 95% 1.17-1.25), thrombotic events (HR 1.55, 95%CI 1.49-1.61), and hemorrhagic events (HR 1.39, 95%CI 1.32-1.46) compared to AF controls (Table 1). On sensitivity analyses, we found that the risk of primary outcomes in AF patients with SAD was independent from the OAC type, but NOAC was more effective than warfarin in reducing the risk of thrombotic events. The highest risk of all-cause death was associated with Systemic Sclerosis, while the highest risk of composite thrombotic events was associated with Systemic Lupus Erythematosus, and Dermato-polymyositis. The highest risk of stroke was associated with Sjogren syndrome; and myocardial infarction and deep vein thrombosis with Dermato-polymyositis, Systemic Lupus Erythematosus was associated with the highest risk of Intracranial hemorrhage, while Systemic Sclerosis to the highest risk of gastrointestinal bleeding (Table 2). Conclusion In AF patients the coexistence of SAD is associated with a high risk of all-cause death, thrombotic events, and bleeding. A personalized approach aimed to minimize the impact of SAD on the clinical course of AF patients is needed.Figure 1Figure 2