Allan J Walkey1, Emily K Quinn2, Michael R Winter2, David D McManus3, Emelia J Benjamin4. 1. Division of Pulmonary and Critical Care Medicine, The Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts2Center of Implementation and Improvement Sciences, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts. 2. Data Coordinating Center, Boston University School of Public Health, Boston, Massachusetts. 3. Section of Cardiac Pacing and Electrophysiology, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester. 4. Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, Massachusetts6Section of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts7Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
Abstract
IMPORTANCE: Atrial fibrillation (AF) during sepsis is associated with an increased risk of ischemic stroke during hospitalization, but risks and benefits associated with anticoagulation for AF during sepsis are unclear. OBJECTIVE: To determine clinician practice patterns and patient risk of stroke and bleeding associated with use of anticoagulation for AF during sepsis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using enhanced administrative claims data from approximately 20% of patients hospitalized in the United States July 1, 2010, to June 30, 2013, examined patients with AF during sepsis who did not have additional indications for therapeutic anticoagulation. Propensity score and instrumental variable analyses were used to evaluate risks of in-hospital stroke and bleeding associated with anticoagulation during sepsis. EXPOSURES: Parenteral anticoagulants administered in doses greater than those used for prophylaxis of venous thromboembolism. MAIN OUTCOMES AND MEASURES: Ischemic stroke and clinically significant bleeding events during hospitalization. RESULTS: Of 113 511 patients hospitalized with AF and sepsis, 38 582 were included in our primary analysis (18 976 men and 19 606 women; mean [SD] age, 74.9 [11.7] years). A total of 13 611 patients (35.3%) received parenteral anticoagulants, while 24 971 (64.7%) did not. Hospital utilization rates of parenteral anticoagulants for AF during sepsis varied (median, 33%; 25th-75th percentile, 25%-43%). CHA2DS2VASc scores (congestive heart failure, hypertension, age ≥75 years [doubled], type 1 or type 2 diabetes, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) poorly discriminated the risk of ischemic stroke during sepsis (C statistic, 0.526). Among 27 010 propensity score-matched patients, rates of in-hospital ischemic stroke events did not differ significantly between patients who did (174 of 13 505 [1.3%]) and did not (185 of 13 505 [1.4%]) receive parenteral anticoagulation (relative risk [RR], 0.94; 95% CI, 0.77-1.15). Clinically significant bleeding occurred more often among patients who received parenteral anticoagulation (1163 of 13 505 [8.6%]) than patients who did not receive parenteral anticoagulation (979 of 13 505 [7.2%]; RR, 1.21; 95% CI, 1.10-1.32). Risk of ischemic stroke associated with parenteral anticoagulation did not differ significantly between patients with preexisting (RR, 1.12; 95% CI, 0.86-1.44) or newly diagnosed AF (RR, 0.85; 95% CI 0.57-1.27; P = .31 for interaction). Results were robust to multiple sensitivity analyses, including hospital utilization rates of parenteral anticoagulation for AF as an instrument for anticoagulation exposure (RR for stroke, 1.08; 95% CI, 0.62-1.90; RR for bleeding, 1.23; 95% CI, 0.88-1.72). CONCLUSIONS AND RELEVANCE: Among patients with AF during sepsis, parenteral anticoagulation was not associated with reduced risk of ischemic stroke and was associated with higher bleeding rates.
IMPORTANCE: Atrial fibrillation (AF) during sepsis is associated with an increased risk of ischemic stroke during hospitalization, but risks and benefits associated with anticoagulation for AF during sepsis are unclear. OBJECTIVE: To determine clinician practice patterns and patient risk of stroke and bleeding associated with use of anticoagulation for AF during sepsis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using enhanced administrative claims data from approximately 20% of patients hospitalized in the United States July 1, 2010, to June 30, 2013, examined patients with AF during sepsis who did not have additional indications for therapeutic anticoagulation. Propensity score and instrumental variable analyses were used to evaluate risks of in-hospital stroke and bleeding associated with anticoagulation during sepsis. EXPOSURES: Parenteral anticoagulants administered in doses greater than those used for prophylaxis of venous thromboembolism. MAIN OUTCOMES AND MEASURES: Ischemic stroke and clinically significant bleeding events during hospitalization. RESULTS: Of 113 511 patients hospitalized with AF and sepsis, 38 582 were included in our primary analysis (18 976 men and 19 606 women; mean [SD] age, 74.9 [11.7] years). A total of 13 611 patients (35.3%) received parenteral anticoagulants, while 24 971 (64.7%) did not. Hospital utilization rates of parenteral anticoagulants for AF during sepsis varied (median, 33%; 25th-75th percentile, 25%-43%). CHA2DS2VASc scores (congestive heart failure, hypertension, age ≥75 years [doubled], type 1 or type 2 diabetes, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) poorly discriminated the risk of ischemic stroke during sepsis (C statistic, 0.526). Among 27 010 propensity score-matched patients, rates of in-hospital ischemic stroke events did not differ significantly between patients who did (174 of 13 505 [1.3%]) and did not (185 of 13 505 [1.4%]) receive parenteral anticoagulation (relative risk [RR], 0.94; 95% CI, 0.77-1.15). Clinically significant bleeding occurred more often among patients who received parenteral anticoagulation (1163 of 13 505 [8.6%]) than patients who did not receive parenteral anticoagulation (979 of 13 505 [7.2%]; RR, 1.21; 95% CI, 1.10-1.32). Risk of ischemic stroke associated with parenteral anticoagulation did not differ significantly between patients with preexisting (RR, 1.12; 95% CI, 0.86-1.44) or newly diagnosed AF (RR, 0.85; 95% CI 0.57-1.27; P = .31 for interaction). Results were robust to multiple sensitivity analyses, including hospital utilization rates of parenteral anticoagulation for AF as an instrument for anticoagulation exposure (RR for stroke, 1.08; 95% CI, 0.62-1.90; RR for bleeding, 1.23; 95% CI, 0.88-1.72). CONCLUSIONS AND RELEVANCE: Among patients with AF during sepsis, parenteral anticoagulation was not associated with reduced risk of ischemic stroke and was associated with higher bleeding rates.
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