Warfarin use and the risks of stroke and bleeding in hemodialysis patients with atrial fibrillation: A systematic review and a meta-analysis

Li, Jingzhen; Wang, Lijuan; Hu, Jinzhu; Xu, Gaosi

doi:10.1016/j.numecd.2015.03.013

Cited by 32 publications

(31 citation statements)

References 36 publications

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“…Multiple observational studies in CKD and dialysis have identified an association between warfarin use and increased risk for embolic stroke and bleeding (41)(42)(43)(44), whereas other studies suggest that warfarin is protective against stroke in this population (45).…”

Section: Rocket-af (Rivaroxaban Once Daily Oral Directmentioning

confidence: 99%

Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF

Chan

Giugliano

Patel

et al. 2016

Journal of the American College of Cardiology

182

172

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Nonvitamin K-dependent oral anticoagulant agents (NOACs) are currently recommended for patients with atrial fibrillation at risk for stroke. As a group, NOACs significantly reduce stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with warfarin. All NOACs are dependent on the kidney for elimination, such that patients with creatinine clearance <25 ml/min were excluded from all the pivotal phase 3 NOAC trials. It therefore remains unclear how or if NOACs should be prescribed to patients with advanced chronic kidney disease and those on dialysis. The authors review the current pharmacokinetic, observational, and prospective data on NOACs in patients with advanced chronic kidney disease (creatinine clearance <30 ml/min) and those on dialysis. The authors frame the evidence in terms of risk versus benefit to bring greater clarity to NOAC-related major bleeding and efficacy at preventing stroke specifically in patients with creatinine clearance <30 ml/min.

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Section: Rocket-af (Rivaroxaban Once Daily Oral Directmentioning

confidence: 99%

Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF

Chan

Giugliano

Patel

et al. 2016

Journal of the American College of Cardiology

182

172

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“…First, this study explicitly identified the population that was limited to patients with AF, who are undergoing dialysis, while Li et al 36 and Liu et al 38 included studies in patients who underwent dialysis and kidney transplant, who had wide variation in their kidney function. Second, Li et al ,36 did not quantify the association between warfarin and mortality outcomes. All of the reviews did not discuss specific stroke risks (ischaemic/haemorrhagic stroke) due to limited data.…”

Section: Discussionmentioning

confidence: 99%

“…9 23-35 Three meta-analyses of observational studies have shown that warfarin therapy had no effect for stroke prevention and mortality, but associated with a higher risk of bleeding in these patients. [36][37][38] The major limitations of the studies included: quantification of the effect of bias from different types of adjustments across studies, limited interpretation by population heterogeneity, outcomes specification and lack of recent published literature.…”

Section: Key Questionsmentioning

confidence: 99%

Efficacy and safety of warfarin in dialysis patients with atrial fibrillation: a systematic review and meta-analysis

et al. 2016

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ObjectiveTo systematically review and meta-analyse the risk–benefit ratio of warfarin users compared with non-warfarin users in patients with atrial fibrillation (AF), who are undergoing dialysis.MethodsWe searched PubMed/MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane Library, grey literature, conference proceedings, trial registrations and also did handsearch. Cohort studies without language restrictions were included. Two investigators independently conducted a full abstraction of data, risk of bias and graded evidence. Effect estimates were pooled using random-effect models.Main outcome measureAll-cause mortality, total stroke/thromboembolism and bleeding complications.Results14 studies included 37 349 dialysis patients with AF, of whom 12 529 (33.5%) were warfarin users. For all-cause mortality: adjusted HR=0.99 (95% CI 0.89 to 1.10; p=0.825), unadjusted risk ratio (RR)=1.00 (95% CI 0.96 to 1.04; p=0.847). For stroke/thromboembolism: adjusted HR=1.06 (95% CI 0.82 to 1.36; p=0.676), unadjusted incidence rate ratio (IRR)=1.23 (95% CI 0.94 to 1.61; p=0.133). For ischaemic stroke/transient ischaemic attack, adjusted HR=0.91 (95% CI 0.57 to 1.45; p=0.698), unadjusted IRR=1.16 (95% CI 0.84 to 1.62; p=0.370). For haemorrhagic stroke, adjusted HR=1.60 (95% CI 0.91 to 2.81; p=0.100), unadjusted IRR=1.48 (95% CI 0.92 to 2.36; p=0.102). Major bleeding was increased among warfarin users; adjusted HR=1.35 (95% CI 1.11 to 1.64; p=0.003) and unadjusted IRR=1.22 (95% CI 1.07 to 1.40; p=0.003).ConclusionsAmong dialysis patients with AF, warfarin therapy was not associated with mortality and stroke/thromboembolism, but significantly increased the risk of major bleeding. More rigorous studies are essential to demonstrate the effect of warfarin for stroke prophylaxis in dialysis patients with AF.

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“…Due to platelet dysfunction, reduced dietary vitamin K intake, altered bioavailability, higher susceptibility to vascular calcifications, HD patients may have a less favorable riskbenefit profile compared to non-ESRD patients with AF [26][27][28][29] . Epidemiological studies seem to corroborate such hypothesis: a recent meta-analysis showed that VKA does not reduce the risk of stroke and increase the risk of bleeding among ESRD patients with AF [24] . The risk-benefit ratio emerging from studies on VKA-related survival are more ambiguous.…”

Section: Discussionmentioning

confidence: 99%

“…Despite oral anticoagulants being the mainstay of treatment for patients with AF without renal impairment, the use of vitamin K antagonists (VKAs) in ESRD is more controversial, given their unclear effect on stroke and mortality risks [6,[12][13][14][15][16][17][18][19][20][21][22][23] , coupled with increased incidence of major bleeding [24] . Concerns with the use of VKAs include initial overdosing due to vitamin K deficiency in ESRD, heparin use during dialysis, impaired platelet and coagulation function, and the possibility that warfarin may increase calcification formation in ESRD patients [25][26][27][28][29] .…”

mentioning

confidence: 99%

Patients' Characteristics Affect the Survival Benefit of Warfarin Treatment for Hemodialysis Patients with Atrial Fibrillation. A Historical Cohort Study

Brancaccio

Neri²,

Bellocchio³

et al. 2016

Am J Nephrol

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Background: Stroke prevention in dialysis-dependent patients with atrial fibrillation (AF) is an unresolved clinical dilemma. Indeed, no randomized controlled trial evaluating the efficacy and safety of oral anticoagulants in this population, has been conducted so far. Observational research on the use of warfarin in patients on dialysis has shown conflicting results. This uncertainty is mirrored by the wide variations in warfarin prescription patterns across centers. We sought to evaluate the association between the use of vitamin K antagonists (VKAs) and mortality among hemodialysis patient with AF and to assess potential factors affecting the risk-benefit profile of warfarin in this population. Methods: A total of 91,987 patients registered in the European Clinical Dialysis Database® system from January 2004 to January 2015. Of which, 9,238 patients were identified with a diagnosis of AF. After excluding ineligible patients, a 1:1 propensity score matched cohort of 1,324 warfarin users and non-users were assembled. Results: VKA use was associated with both increased 90-day survival (hazard ratio, HR 0.47, p < 0.01) and 6-year survival (HR 0.76, p < 0.01); however, a trend indicated a stronger early benefit (p for time-interaction <0.01). Moderation analysis showed that patients' age and clinical history of stroke strongly influenced warfarin-related benefits on survival. Conclusion: VKA may provide an early survival benefit; however, this is partially offset later during the follow-up. In addition, heterogeneous risk-benefit profiles were observed among subgroups of dialysis-dependent patients with AF, further emphasizing the complexities of tailoring stroke prevention strategies in this population.

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Warfarin use and the risks of stroke and bleeding in hemodialysis patients with atrial fibrillation: A systematic review and a meta-analysis

Cited by 32 publications

References 36 publications

Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF

Nonvitamin K Anticoagulant Agents in Patients With Advanced Chronic Kidney Disease or on Dialysis With AF

Efficacy and safety of warfarin in dialysis patients with atrial fibrillation: a systematic review and meta-analysis

Patients' Characteristics Affect the Survival Benefit of Warfarin Treatment for Hemodialysis Patients with Atrial Fibrillation. A Historical Cohort Study

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