Severe renal dysfunction among individuals taking warfarin and implications for new oral anticoagulants
Cove, Christina Lauren
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BACKGROUND: Although novel anticoagulant drugs have proven safety and efficacy profiles from Phase III clinical trials, those patients with significant kidney disease were excluded. The lack of knowledge about incidence, severity and risk factors for severe renal dysfunction in patients requiring oral anticoagulation impedes development of strategies to mitigate risks of hemorrhage associated with renally-eliminated novel oral anticoagulants. METHODS: Patients taking warfarin for atrial fibrillation (AF) or venous thromboembolism (VTE) were consecutively enrolled from January 2007 to December 2010. Baseline kidney function was assessed and patients were followed to their first decline in Glomerular Filtration Rate (GFR) to < 30 ml/min estimated by the Cockcroft-Gault calculation. Independent risk factors for development of severe kidney dysfunction were assessed by multivariate analysis. RESULTS: Of 787 patients identified, 34 were excluded for baseline eGFR < 30 ml/min. The mean age of the cohort was 71 years. At baseline, 23% (n=174) had moderate renal impairment, or Stage 3 CKD (eGFR 30-59 ml/min), while 31% had mild disease. Overall, those with hypertension, congestive heart failure (CHF), diabetes mellitus (DM), and coronary artery disease (CAD) were 74%, 33%, 31%, 24%, and 9% of the cohort, respectively. A decline in eGFR to < 30 ml/min (the primary outcome) occurred in 91 patients, 25% of which happened within 5.3 months. Of those with baseline Stage 3 CKD, 37% experienced the primary outcome. In multiple logistic regression analysis, a baseline eGFR 30–59 ml/min conferred a greater than 14-fold increased risk in the development of eGFR < 30 ml/min (OR 14.5, 99% CI: 5.3 to 39.8, P<0.001) during the warfarin exposure period. CAD was associated with a greater than two-fold increased risk (OR 2.2, 95% CI 1.1 to 4.4, P=0.004). After adjusting for baseline kidney function, age was not an independent risk factor for a decline in eGFR to < 30 ml/min. CONCLUSIONS: Acute and chronic renal dysfunction is common among individuals on chronic warfarin therapy. Better understanding of the fluctuations in renal function would inform patient selection and monitoring strategies for optimal use of novel anticoagulants.
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