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Warfarin Use and Increased Mortality in End-Stage Renal Disease
Mark C Lin1, Elani Streja, Melissa Soohoo
1School of Medicine, University of California, Irvine, CA, USA.
Insights
Warfarin therapy significantly increases mortality, bleeding, and heart attack risks in dialysis patients. These findings suggest reconsidering warfarin use in this vulnerable population.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Controversy surrounds warfarin use in chronic kidney disease (CKD) and end-stage renal disease (ESRD).
- Assessing warfarin's impact on mortality and cardiovascular outcomes in CKD/ESRD patients is crucial.
Purpose of the Study:
- To evaluate the risks of warfarin therapy in patients with stages 3-5 CKD and ESRD.
- To compare mortality and cardiovascular events between warfarin users and non-users in this cohort.
Main Methods:
- Retrospective matched cohort study of 59 warfarin users and 144 non-users with stages 3-6 CKD.
- Cox regression for mortality risk; Poisson regression for bleeding and cardiovascular events.
- Adjusted for confounders and stratified by CKD stage (3-5 vs. ESRD).
Main Results:
- Warfarin use was associated with higher unadjusted mortality (HR 2.34).
- Adjusted analysis showed significantly higher mortality in ESRD patients on warfarin (HR 6.62).
- Warfarin users had increased risks of significant bleeding (IRR 3.57) and myocardial infarction (IRR 4.20).
Conclusions:
- Warfarin is linked to substantially increased risks of death, bleeding, and myocardial infarction in dialysis patients.
- The use of warfarin in dialysis patients requires urgent re-evaluation based on these findings.
Background:
Controversy exists regarding the benefits and risks of warfarin therapy in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In this study, we assessed mortality and cardiovascular outcomes associated with warfarin treatment in patients with stages 3-5 CKD and ESRD admitted to the University of California-Irvine Medical Center.
Methods:
In a retrospective matched cohort study, we identified 59 adult patients with stages 3-6 CKD initiated on warfarin during the period 2011-2013, and 144 patients with stages 3-6 CKD who had indications for anticoagulation therapy but were not initiated on warfarin. All-cause mortality risk associated with warfarin treatment was estimated using Cox proportional hazard regression analysis, and the risk of significant bleeding and major adverse cardiovascular events were analyzed with Poisson regression analysis. Adjustment models were used to account for age, gender, diabetes mellitus, use of antiplatelet agents, and preexisting cardiovascular disease, and stratified by pre-dialysis CKD stages 3-5 vs. ESRD.
Findings:
During 5.8 years of follow-up, unadjusted mortality risk was higher in CKD patients on warfarin therapy (hazard ratio [HR] 2.34 with 95% CI 1.25-4.39; p < 0.01). After multivariate adjustment and stratification by CKD stage, the mortality risk remained significant in ESRD patients receiving warfarin (HR 6.62 with 95% CI 2.56-17.16; p < 0.001). Furthermore, adjusted rates of significant bleeding (incident rate ratio, IRR 3.57 with 95% CI 1.51-8.45; p < 0.01) and myocardial infarction (IRR 4.20 with 95% CI 1.78-9.91; p < 0.01) were higher among warfarin users. No differences in rates of ischemic or hemorrhagic strokes were found between the 2 groups.
Conclusions:
Warfarin use was associated with several-fold higher risk of death, bleeding, and myocardial infarction in dialysis patients. If additional studies suggest similar associations, the use of warfarin in dialysis patients warrants immediate reconsideration.
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