Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation

• IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24 317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m(2) [eGFR(<60)]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR(>30-60): event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR(>15-30): event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR(<= 15): event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR(>30-60) event rate, 6.8 forwarfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR(>15-30) event rate, 9.3 forwarfarin vs 10.4 for nowarfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR(<= 15) event rate, 9.1 forwarfarin vs 13.5 for nowarfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR(>60) event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR(>30-60) event rate, 53.6 forwarfarin vs 69.0 for nowarfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR(>15-30) event rate, 90.2 forwarfarin vs 117.7 for nowarfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR(<= 15) event rate, 86.2 forwarfarin vs 138.2 for nowarfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.

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