Warfarin and the Risk of Death, Stroke, and Major Bleeding in Patients With Atrial Fibrillation Receiving Hemodialysis: A Systematic Review and Meta-Analysis

Abstract

Background: Up to date, the efficacy and safety of warfarin treatment in atrial fibrillation patients receiving hemodialysis remain controversial. So we performed this meta-analysis to try to offer recommendations regarding warfarin management in this population.Methods: We searched Pubmed, Embase, and Cochrane library and reviewed relevant reference lists from 1980 to March 2018. Studies were included if they described the risks of mortality, stroke, and bleeding events with or without warfarin in atrial fibrillation patients receiving hemodialysis.Results: Overall, the use of warfarin was not associated with mortality (OR = 0.95, 95%CI = 0.89–1.02), stroke (OR = 1.06, 95% CI = 0.87–1.30) and ischemic stroke (OR = 0.85, 95% CI = 0.68–1.05), but its use could increase the risks of hemorrhagic stroke (OR = 1.34, 95% CI = 1.13–1.59) and major bleeding (OR = 1.24, 95% CI = 1.14, 1.35). In subgroup analyses, when analyses were mainly restricted to atrial fibrillation patients who were undergoing hemodialysis and taking other anticoagulation agents, warfarin therapy didn't reduce the risks for mortality (OR = 0.98, 95% CI = 0.68–1.42) and ischemic stroke (OR = 1.03, 95% CI = 0.89–1.19), but significantly increased the risks of stroke (OR:1.14, 95% CI = 1.01–1.29) and bleeding events such as hemorrhagic stroke (OR = 1.42, 95% CI = 1.14–1.77) and major bleeding (OR = 1.24, 95% CI = 1.14–1.35). While in patients who didn't take other anticoagulation agents or aspirin, warfarin use was not associated with all-cause mortality (OR = 0.90, 95% CI = 0.78–1.04), or any stroke (OR = 1.00, 95% CI = 0.71–1.40). Its use was associated with significantly decreased risk of ischemic stroke (OR = 0.71, 95% CI = 0.60–0.85), but not associated with hemorrhagic stroke (OR = 1.45, 95% CI = 0.83–2.55). Besides, another subgroup analysis showed that warfarin therapy didn't exert a protective role in patients with normal serum lipid levels (OR = 1.04, 95% CI = 0.85–1.26), but seemed to decrease the risk of ischemic stroke in patients with hyperlipidemia (OR = 0.38, 95% CI = 0.11–1.29).Conclusion: Our results suggested that it was necessary to prescribe warfarin for the prevention of ischemic events in hemodialysis patients with atrial fibrillation, but if these patients were already prescribed with other anticoagulants for the treatment of other co-existing diseases, then warfarin was not recommended.

Association Between Use of Warfarin for Atrial Fibrillation and Outcomes Among Patients With End-Stage Renal Disease

“…In the contemporary period, several meta-analyses have been performed in different parts of the world . With the latest studies, our data substantiate the results of these analyses, suggesting that there is no association between warfarin use for patients with ESRD and AF and protection against ischemic strokes but rather an association between warfarin use and a higher risk of hemorrhagic stroke .…”

“…In the contemporary period, several meta-analyses have been performed in different parts of the world. 7,[24][25][26][27][28][29][30][31][32] With the latest studies, our data substantiate the results of these analyses, suggesting that there is no association between warfarin use for patients with ESRD and AF and protection against ischemic strokes but rather an association between warfarin use and a higher risk of hemorrhagic stroke. 15,[24][25][26]28 Lee et al, 26 Lui et al, 24 and Nochaiwong et al 27 showed that there was no association of warfarin use with ischemic stroke and mortality but that there was an association of warfarin use with an increased risk of hemorrhagic stroke and major bleeding.…”

“…Notably, to our knowledge, no randomized clinical trials have examined the role of anticoagulation in patients with ESRD and AF, and periodically performed meta-analyses have provided inconsistent results. 7,[24][25][26][27][28][29][30][31][32] This inconsistency has even prevailed in the guidelines from various societies. Where the American Heart Association/American College of Cardiology guideline 1 recommends anticoagulation in patients with ESRD and AF, the European Cardiovascular Society guideline 33 emphasizes the lack of evidence for such a recommendation, and the Kidney Disease:…”

“…Several studies have investigated the effectiveness and outcomes of warfarin in preventing ischemic strokes in patients with ESRD and AF; most have been either observational or retrospective, and very few have been prospective. Notably, to our knowledge, no randomized clinical trials have examined the role of anticoagulation in patients with ESRD and AF, and periodically performed meta-analyses have provided inconsistent results . This inconsistency has even prevailed in the guidelines from various societies.…”

Clinical Interventions and All-Cause Mortality of Patients with Chronic Kidney Disease: An Umbrella Systematic Review of Meta-Analyses

“…This was reflected in discordant recommendations, whereby one guideline did not recommend anticoagulant use for dialysis patients [47], and the other recommended warfarin but not new oral anticoagulants based on observational data [48]. However, the mortality benefit of warfarin in dialysis patients did not reach statistical significance in a meta-analysis of OSs [49]. In RCTs of anticoagulants, people with CKD and ESRD are frequently excluded [50,51].…”