Original Investigation
Dialysis
Outcomes After Warfarin Initiation in a Cohort of Hemodialysis Patients With Newly Diagnosed Atrial Fibrillation

https://doi.org/10.1053/j.ajkd.2015.05.019Get rights and content

Background

Although warfarin is indicated to prevent ischemic strokes in most patients with atrial fibrillation (AF), evidence supporting its use in hemodialysis patients is limited. Our aim was to examine outcomes after warfarin therapy initiation, relative to no warfarin use, following incident AF in a large cohort of hemodialysis patients who had comprehensive prescription drug coverage through Medicare Part D.

Study Design

Retrospective observational cohort study.

Setting & Participants

Patients in the US Renal Data System undergoing maintenance hemodialysis who had AF newly diagnosed in 2007 to 2011, with Medicare Part D coverage, who had no recorded history of warfarin use.

Predictor

Warfarin therapy initiation, identified by a filled prescription within 30 days of the AF event.

Outcomes

Death, ischemic stroke, hemorrhagic stroke, severe gastrointestinal bleeding, and composite outcomes.

Measurements

HRs estimated by applying Cox regression to an inverse probability of treatment and censoring-weighted cohort.

Results

Of 12,284 patients with newly diagnosed AF, 1,838 (15%) initiated warfarin therapy within 30 days; however, ∼70% discontinued its use within 1 year. In intention-to-treat analyses, warfarin use was marginally associated with a reduced risk of ischemic stroke (HR, 0.68; 95% CI, 0.47-0.99), but not with the other outcomes. In as-treated analyses, warfarin use was associated with reduced mortality (HR, 0.84; 95% CI, 0.73-0.97).

Limitations

Short observation period, limited number of nonfatal events, limited generalizability of results to more affluent patients.

Conclusions

In hemodialysis patients with incident AF, warfarin use was marginally associated with reduced risk of ischemic stroke, and there was a signal toward reduced mortality in as-treated analyses. These results support clinical equipoise regarding the use of warfarin in hemodialysis patients and underscore the need for randomized trials to fill this evidence gap.

Section snippets

Study Population

From the US Renal Data System (USRDS), we identified all hemodialysis patients who had a new diagnosis of AF in July 2007 to December 2011 based on 1 inpatient or 2 outpatient diagnosis codes within 30 days of each other indicating AF or atrial flutter (International Classification of Diseases, Ninth Revision codes 427.3x; Fig 1). We excluded those with a history of valvular disease associated with AF (Table S1, available as online supplementary material).11 For patients with AF diagnosed from

Patient Characteristics

We identified 12,284 patients undergoing hemodialysis who had AF newly diagnosed, 15% of whom initiated warfarin therapy (Fig 1). Users and nonusers differed only slightly, and most of these differences were related to risk factors for bleeding (Table 1). Notably, 90% of both groups met CHADS2 criteria for oral anticoagulation for patients with AF (score ≥ 2), although a larger proportion of nonusers (70% vs 63%) had a HAS-BLED score ≥ 3, a situation in which anticoagulation is not recommended

Discussion

The benefits of oral anticoagulation for AF have been demonstrated in a number of randomized trials22; however, patients with ESRD were excluded from these studies. Therefore, whether the benefits of oral anticoagulation extend to patients undergoing hemodialysis is unclear23, 24, 25 because they have a substantially higher risk of stroke compared with the general population, but also a higher risk of bleeding.13, 23, 24, 25, 26 This clinical equipoise was reflected in a survey of Canadian

Acknowledgements

Data reported here were supplied by the USRDS. Interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government.

Support: This work was supported by grants F32DK096765 (Dr Shen), K23DK095914 (Dr Chang), and R21DK077336 and R01DK095024 (Dr Winkelmayer) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD. The Stanford Nephrology fellowship program was

References (36)

  • B.A. Goldstein et al.

    Trends in the incidence of atrial fibrillation in older patients initiating dialysis in the United States

    Circulation

    (2012)
  • J.P. Piccini et al.

    Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries, 1993-2007

    Circulation Cardiovasc Qual Outcomes

    (2012)
  • V. Fuster et al.

    ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society

    Circulation

    (2006)
  • K.E. Chan et al.

    Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation

    J Am Soc Nephrol

    (2009)
  • W.C. Winkelmayer et al.

    Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation

    Clin J Am Soc Nephrol

    (2011)
  • M. Shah et al.

    Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis

    Circulation

    (2014)
  • T.I. Chang et al.

    Multivessel coronary artery bypass grafting versus percutaneous coronary intervention in ESRD

    J Am Soc Nephrol

    (2012)
  • J.Y. Yang et al.

    Trends in acute nonvariceal upper gastrointestinal bleeding in dialysis patients

    J Am Soc Nephrol

    (2012)
  • Cited by (0)

    Because an author of this article is an editor for AJKD, the peer-review and decision-making processes were handled entirely by an Associate Editor (Csaba P. Kovesdy, MD) who served as Acting Editor-in-Chief. Details of the journal’s procedures for potential editor conflicts are given in the Information for Authors & Journal Policies.

    View full text