Practice Patterns and Outcomes Associated With Use of Anticoagulation Among Patients With Atrial Fibrillation During Sepsis

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 st...

Bleeding Complications in Anticoagulated Patients With Atrial Fibrillation and Sepsis: A Propensity‐Weighted Cohort Study

“…In a small study of 115 older adult patients with preexisting AF, Darwish et al observed no ischemic strokes and only 3 bleeding events in 35 patients with OACs versus none in patients without OACs. Recently, Walkey et al showed an increased risk of in‐hospital bleeding events in AF patients receiving parenteral anticoagulation during sepsis compared with propensity‐matched patients receiving no anticoagulation (8.6% versus 7.2%; relative risk: 1.21; 95% CI, 1.10–1.32). In this study, ≈80% of the patients had preexisting AF, in whom bleeding risk was lower than in patients with new‐onset AF (6.7% versus 12.6%) .…”

“…Recently, Walkey et al showed an increased risk of in‐hospital bleeding events in AF patients receiving parenteral anticoagulation during sepsis compared with propensity‐matched patients receiving no anticoagulation (8.6% versus 7.2%; relative risk: 1.21; 95% CI, 1.10–1.32). In this study, ≈80% of the patients had preexisting AF, in whom bleeding risk was lower than in patients with new‐onset AF (6.7% versus 12.6%) . Nonetheless, it is difficult to determine whether this bleeding risk is substantial enough to warrant concern; some excess bleeding among warfarin users would be expected compared with warfarin nonusers.…”

“…In this study, 80% of the patients had preexisting AF, in whom bleeding risk was lower than in patients with new-onset AF (6.7% versus 12.6%). 6 Nonetheless, it is difficult to determine whether this bleeding risk is substantial enough to warrant concern; some excess bleeding among warfarin users would be expected compared with warfarin nonusers. In line with our findings, Walkey et al 6 reported comparable rates of thromboembolic events among AF patients with anticoagulation compared with matched comparisons with no anticoagulation.…”

“…Concerns about anticoagulation therapy in sepsis patients underscore the importance of assessing bleeding risk in patients whose home medications include oral anticoagulant (OAC) therapy. Two prior studies have indicated that anticoagulant therapy is associated with an increased risk of bleeding in AF patients during sepsis . However, there is a lack of large‐scale, population‐based assessments of outcomes in sepsis patients with preexisting atrial fibrillation (AF) on continuous anticoagulant therapy.…”

“…Two prior studies have indicated that anticoagulant therapy is associated with an increased risk of bleeding in AF patients during sepsis. 5,6 However, there is a lack of large-scale, population-based assessments of outcomes in sepsis patients with preexisting atrial fibrillation (AF) on continuous anticoagulant therapy. In a prior US study of Medicare beneficiaries, AF occurred in 25% of patients with hospitalized sepsis, of which 18% had preexisting AF.…”