Elsevier

American Heart Journal

Volume 184, February 2017, Pages 37-46
American Heart Journal

Clinical Investigation
Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: A systematic review and meta-analysis

https://doi.org/10.1016/j.ahj.2016.09.016Get rights and content

Background

The use of vitamin K antagonists (VKAs) in hemodialysis patients with atrial fibrillation (AF) is controversial. No randomized trials are available and observational studies have yielded conflicting results, engendering a large clinical practice variability and physician uncertainty. An unresolved but highly relevant question is whether AF poses a true risk of ischemic stroke in hemodialysis and whether any form of oral anticoagulation is therefore warranted.

Methods

We conducted a systematic review of studies that compared the incidence of ischemic stroke and bleeding in hemodialysis patients with AF taking VKA and those not taking VKA. When hemodialysis patients had been pooled with peritoneal dialysis, kidney transplant, or stage V chronic kidney disease patients, unpublished outcome data of the hemodialysis subgroup were obtained through personal communication. The main outcome measures were ischemic stroke/thromboembolic events, all-cause mortality, major bleeding, and hemorrhagic stroke. Combined hazard ratios (HRs) and 95% CIs were calculated using a random-effects model.

Results

Twelve prospective or retrospective cohort studies were included in the meta-analysis, totaling 17,380 hemodialysis patients of whom 4,010 (23.1%) received VKA. In VKA-treated patients, mean CHADS2 or CHA2DS2VASc score was low (range 1.7-2.75) or a sizeable proportion of patients had scores <2 (range 2%-23%). Time in the therapeutic range or mean international normalized ratio was generally low. Treatment with VKA was associated with a nonsignificant 26% reduction of the risk of ischemic stroke (HR 0.74; 0.51-1.06), a 21% increase in total bleeding risk (HR 1.21; 1.03-1.43), and no effect on mortality (HR 1.00; 0.92-1.09). Vitamin K antagonist almost doubled the risk of hemorrhagic stroke, but this did not reach the limit of statistical significance (4 studies, n = 16.365; HR 1.93; 0.93-3.98).

Conclusion

Our meta-analysis revealed a trend for a reduction of the risk of ischemic stroke in hemodialysis patients with AF treated with VKA. The true protective effect may have been underestimated, owing to inclusion of low-risk patients not expected to benefit from anticoagulation and to suboptimal anticoagulation. However, assessment of the overall effect of VKA in hemodialysis patients should also take into account the increased risk of bleeding, in particular of hemorrhagic stroke. Whether new oral anticoagulants provide a better benefit-risk ratio in hemodialysis patients should be the subject of future trials.

Section snippets

Search strategy and study selection

A search was performed in PubMed, EMBASE, and the Cochrane Library Database from inception to December 2015. Guidelines from scientific committees (American Heart Association/American College of Cardiology, Kidney Disease Improving Global Outcomes, Kidney Disease Outcomes Quality Initiative, Canadian Cardiovascular Society, European Society of Cardiology) and reference lists of identified articles were also reviewed. The list of titles and abstracts was assessed by 2 investigators to identify

Search results

The literature search identified 233 potentially relevant reports. Of these, 210 were excluded based on title and abstract review (Figure 1). After full review, 11 further reports were excluded: 4 for incomplete data, 1 for absence of stroke characterization, 2 for unavailability of outcome data on the hemodialysis subgroup, and 3 for prescription of VKA for other indications than AF. The study by Olesen et al21 was excluded for a complete overlap of the study population (Danish National

Discussion

In the past few years, the use of VKA in hemodialysis patients with AF has been the subject of an unresolved debate. The primary aim of this systematic review and meta-analysis was to evaluate whether VKA protect hemodialysis patients with AF against ischemic stroke and systemic embolism.

A first and important strength of our study is that we exclusively incorporated data obtained in hemodialysis patients. Thrice weekly anticoagulation during hemodialysis may protect against stroke. Patients

Acknowledgements

We are greatly indebted to Anders Nissen Bonde (MB, Copenhagen University Hospital Gentofte, Denmark), Lina Benson and Leif Friberg (PhD, MD, Karolinska Institutet and Cardiology Clinic, Stockholm, Sweden), Hoang Lai (MD, New York Medical College, Valhalla, NY), Louise Pilote (MD, MPH, PhD, McGill University Health Centre, Quebec, Canada), and Tom Wang (MBChB, Auckland City Hospital, New Zealand) for providing us with unpublished data on the hemodialysis subgroup of their study.

References (41)

  • C.L. Morgan et al.

    Warfarin treatment in patients with atrial fibrillation: observing outcomes associated with varying levels of INR control

    Thromb Res

    (2009)
  • A.S. De Vriese et al.

    Dose-finding study of rivaroxaban in hemodialysis patients

    Am J Kidney Dis

    (2015)
  • T.F. Chao et al.

    Incidence and prediction of ischemic stroke among atrial fibrillation patients with end-stage renal disease requiring dialysis

    Heart Rhythm

    (2014)
  • J. Li et al.

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

    Nutr Metab Cardiovasc Dis

    (2015)
  • K. Dahal et al.

    Stroke, major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studies

    Chest

    (2016)
  • D. Zimmerman et al.

    Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis

    Nephrol Dial Transplant

    (2012)
  • W. Herrington et al.

    Evidence for the prevention and treatment of stroke in dialysis patients

    Semin Dial

    (2015)
  • R. Caluwé et al.

    The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: ongoing randomized controlled trials

    Clin Kidney J

    (2016)
  • S. Juma et al.

    Warfarin use in hemodialysis patients with atrial fibrillation: decisions based on uncertainty

    BMC Nephrol

    (2013)
  • P.J. Phelan et al.

    Warfarin use in hemodialysis patients: what is the risk?

    Clin Nephrol

    (2011)
  • Cited by (84)

    • Bleeding Risk in Hemodialysis Patients

      2024, Seminars in Nephrology
    View all citing articles on Scopus

    Conflict of interest statement: The results presented in this paper have not been published previously in whole or part.

    View full text