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Original Investigation |

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

Juan Jesús Carrero, PhD(Pharm and Med)1,2; Marie Evans, MD, PhD2; Karolina Szummer, MD, PhD3; Jonas Spaak, MD, PhD4; Lars Lindhagen, PhD5; Robert Edfors, MD3; Peter Stenvinkel, MD, PhD2; Stefan H Jacobson, MD, PhD4; Tomas Jernberg, MD, PhD3
[+] Author Affiliations
1Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
2Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden
3Division of Cardiology, Karolinska Institutet, Stockholm, Sweden
4Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
5Uppsala Clinical Research Center, Sweden
JAMA. 2014;311(9):919-928. doi:10.1001/jama.2014.1334.
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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 m2 [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); eGFR15: 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 for warfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR>15-30 event rate, 9.3 for warfarin vs 10.4 for no warfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR15 event rate, 9.1 for warfarin vs 13.5 for no warfarin; 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 for warfarin vs 69.0 for no warfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR>15-30 event rate, 90.2 for warfarin vs 117.7 for no warfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR15 event rate, 86.2 for warfarin vs 138.2 for no warfarin; 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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Figure 1.
Kaplan-Meier Curves for Individuals With Differing Degrees of Renal Function Stratified by Warfarin Use

Panels A and C depict the cumulative incidence curves for patients according to chronic kidney disease stages. Panels B and D stratify chronic kidney disease stages by warfarin exposure. Y-axis scale segments in blue indicate range from 0.0 to 0.14.

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Figure 2.
Kaplan-Meier Curves for Individuals With Differing Degrees of Renal Function Stratified by Warfarin Use

Panel A depicts the cumulative incidence curves for patients according to chronic kidney disease stages. Panel B stratifies chronic kidney disease stages by warfarin exposure.

Graphic Jump Location

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