Patients with severe chronic kidney disease on warfarin therapy had a more than two-fold higher risk for major hemorrhage compared to patients with lesser degrees of renal dysfunction (HR 2.4).
Cohort (n=565)
Single-blind (outcome adjudicator blinded to genotype)
Yes
Does severe chronic kidney disease increase the risk of hemorrhagic complications and alter warfarin dosage requirements compared to normal or mild kidney function in patients on warfarin?
Patients with severe CKD require lower warfarin doses, have poorer anticoagulation control, and face a significantly higher risk of major hemorrhage, suggesting a need for lower initiation doses and closer monitoring.
Effect estimate: HR 2.4 (95% CI 1.1 to 5.3)
Absolute Event Rate: 30.5% vs 6.2%
p-value: p=0.027
Although management of warfarin is challenging for patients with chronic kidney disease (CKD), no prospective studies have compared response to warfarin among patients with minimal, moderate, and severe CKD. This secondary analysis of a prospective cohort of 578 patients evaluated the influence of kidney function on warfarin dosage, anticoagulation control, and risk for hemorrhagic complications. We adjusted all multivariable regression and proportional hazard analyses for clinical and genetic factors. Patients with severe CKD (estimated GFR 4; P = 0.052), compared with patients with no, mild, or moderate CKD. Patients with severe CKD had a risk for major hemorrhage more than double that of patients with lesser degrees of renal dysfunction (hazard ratio 2.4, 95% confidence interval 1.1 to 5.3). In conclusion, patients with reduced kidney function require lower dosages of warfarin, have poorer control of anticoagulation, and are at a higher risk for major hemorrhage. These observations suggest that warfarin may need to be initiated at a lower dosage and monitored more closely in patients with moderate or severe CKD compared with the general population. Diminished renal function may have implications for a larger proportion of warfarin users than previously estimated.
Limdi et al. (2009) conducted a cohort in Chronic kidney disease requiring warfarin therapy (n=565). Severe chronic kidney disease (eGFR <30 ml/min/1.73m2) vs. No/mild chronic kidney disease (eGFR ≥60 ml/min/1.73m2) was evaluated on Major hemorrhage (HR 2.4, 95% CI 1.1 to 5.3, p=0.027). Patients with severe chronic kidney disease on warfarin therapy had a more than two-fold higher risk for major hemorrhage compared to patients with lesser degrees of renal dysfunction (HR 2.4).