Skip to main content

Advertisement

SpringerLink
Log in

Effect of oral anticoagulant therapy on mortality in end-stage renal disease patients with atrial fibrillation: a prospective study

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to evaluate, in a cohort of haemodialysis patients with atrial fibrillation (AF), the relationship between oral anticoagulant therapy (OAT) and mortality, thromboembolic events and haemorrhage.

Methods

Two hundred and ninety patients with AF were prospectively followed for 4 years. Warfarin and antiplatelet intake, age, dialytic age, comorbidities, CHA2DS2-VASc and HAS-BLED scores were considered as predictors of risk of death, thromboembolism and bleeding events. In patients taking OAT, the international normalized ratio (INR) was assessed and the percentage time in the target therapeutic range (TTR) was calculated.

Results

At recruitment, 134/290 patients were taking warfarin. During follow-up there were 170 deaths, 28 thromboembolic events and 95 bleedings. After balancing for treatment propensity, intention-to-treat analysis on OAT intake at recruitment did not show differences in total mortality, thromboembolic events and bleedings, while the as-treated analysis, accounting for treatment switch, showed that patients taking OAT at recruitment had a significantly lower mortality than those not taking it [hazard ratio, HR 0.53 (95% confidence interval 0.28–0.90), p = 0.04], with a decrease of thromboembolic events [HR 0.36 (0.13–1.05), p = 0.06], and an increase of bleedings [HR 1.79 (0.72–4.39), p = 0.20], both non-significant. Among patients taking OAT at recruitment, those continuing to take warfarin had a significant reduction in the risk of total [HR 0.28 (0.14–0.53), p < 0.001] and cardiovascular [HR 0.21 (0.11–0.40), p < 0.001] mortality compared to patients stopping OAT.

Conclusions

In haemodialysis patients with AF, continuously taking warfarin is associated with a reduction of the risk of total and cardiovascular mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Chan KE, Lazarus JM, Thadhani R et al (2009) Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol 20:2223–2233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shah M, Avgil Tsadok M, Jackevicius CA et al (2014) Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 129:1196–1203

    Article  CAS  PubMed  Google Scholar 

  3. Olesen JB, Lip GY, Kamper AL et al (2012) Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 367:625–635

    Article  CAS  PubMed  Google Scholar 

  4. Carrero JJ, Evans M, Szummer K et al (2014) Warfarin, kidney dysfunction, and outcomes following acute myocardial infarction in patients with atrial fibrillation. J Am Med Assoc 311:919–928

    Article  CAS  Google Scholar 

  5. Genovesi S, Rossi E, Pogliani D et al (2014) The nephrologist’s anticoagulation treatment patterns/regimens in chronic hemodialysis patients with atrial fibrillation. J Nephrol 27:187–192

    Article  CAS  PubMed  Google Scholar 

  6. Shen JI, Montez-Rath ME, Lenihan CR et al (2015) Outcomes after warfarin initiation in a cohort of hemodialysis patients with newly diagnosed atrial fibrillation. Am J Kidney Dis 66:677–688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Genovesi S, Rossi E, Gallieni M et al (2015) Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation. Nephrol Dial Transplant 30:491–498

    Article  PubMed  Google Scholar 

  8. Camm AJ, Lip GY, De Caterina R et al (2012) 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33:2719–2747

    Article  PubMed  Google Scholar 

  9. Rosendaal FR, Cannegieter SC, van der Meer FJ et al (1993) A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 69:236–239

    CAS  PubMed  Google Scholar 

  10. Hernán MA, Brumback B, Robins JM (2000) Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 11:561–570

    Article  PubMed  Google Scholar 

  11. Austin PC (2009) Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 28:3083–3107

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gran JM, Røysland K, Wolbers M et al (2010) A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study. Stat Med 29:2757–2768

    Article  PubMed  Google Scholar 

  13. Pisters R, Lane DA, Nieuwlaat R et al (2010) A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 138:1093–1100

    Article  PubMed  Google Scholar 

  14. Chan KE, Lazarus JM, Thadhani R et al (2009) Anticoagulant and antiplatelet usage associates with mortality among hemodialysis patients. J Am Soc Nephrol 20:872–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sood MM, Larkina M, Thumma JR et al (2013) Major bleeding events and risk stratification of antithrombotic agents in hemodialysis: results from the DOPPS. Kidney Int 84:600–608

    Article  CAS  PubMed  Google Scholar 

  16. Bonde AN, Lip GY, Kamper AL et al (2014) Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol 64:2471–2482

    Article  CAS  PubMed  Google Scholar 

  17. Chen JJ, Lin LY, Yang YH et al (2014) Anti-platelet or anti-coagulant agent for the prevention of ischemic stroke in patients with end-stage renal disease and atrial fibrillation-a nation-wide database analyses. Int J Cardiol 177:1008–1011

    Article  PubMed  Google Scholar 

  18. Fusaro M, Gallieni M, Rebora P,et al (2016) Atrial fibrillation and low vitamin D levels are associated with severe vascular calcifications in hemodialysis patients. J Nephrol 29:419–426

    Article  CAS  PubMed  Google Scholar 

  19. Shih CJ, Ou SM, Chao PW et al (2016) Risks of death and stroke in patients undergoing hemodialysis with new-onset atrial fibrillation: a competing-risk analysis of a nationwide cohort. Circulation 133:265–272

    CAS  PubMed  Google Scholar 

  20. Genovesi S, Vincenti A, Rossi E et al (2008) Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis 51:255–262

    Article  PubMed  Google Scholar 

  21. Wizemann V, Tong L, Satayathum S et al (2010) Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 77:1098–1106

    Article  CAS  PubMed  Google Scholar 

  22. Seliger SL, Gillen DL, Longstreth WT et al (2003) Elevated risk of stroke among patients with end-stage renal disease. Kidney Int 64:603–609

    Article  PubMed  Google Scholar 

  23. Ng KP, Edwards NC, Lip GY et al (2013) Atrial fibrillation in CKD: balancing the risks and benefits of anticoagulation. Am J Kidney Dis 62:615–632

    Article  PubMed  Google Scholar 

  24. Anand SS, Yusuf S (2003) Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol 41:62S–69S

    Article  CAS  PubMed  Google Scholar 

  25. Lamberts M, Gislason GH, Lip GY et al (2014) Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation 129:1577–1585

    Article  CAS  PubMed  Google Scholar 

  26. Pilotto A, Gallina P, Copetti M et al (2016) Warfarin treatment and all-cause mortality in community-dwelling older adults with atrial fibrillation: a retrospective observational study. J Am Geriatr Soc 64:1416–1424

    Article  PubMed  Google Scholar 

  27. Brancaccio D, Neri L, Bellocchio F et al (2016) Patients’ characteristics affect the survival benefit of warfarin treatment for hemodialysis patients with atrial fibrillation. A historical cohort study. Am J Nephrol 44:258–267

    Article  CAS  PubMed  Google Scholar 

  28. Reddy VY, Sievert H, Halperin J et al (2014) Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. J Am Med Assoc 312:1988–1998

    Article  Google Scholar 

  29. Zimmerman D, Sood MM, Rigatto C, Holden RM, Hiremath S, Clase CM (2012) Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis. Nephrol Dial Transplant 27:3816–3822

    Article  CAS  PubMed  Google Scholar 

  30. Danaei G, Tavakkoli M, Hernán MA (2012) Bias in observational studies of prevalent users: lessons for comparative effectiveness research from a meta-analysis of statins. Am J Epidemiol 175:250–262

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

PR was supported by the Grant SIR RBSI14LOVD of the Italian Ministry of Education, University and Research.

Author information

Authors and Affiliations

  1. Department of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900, Monza (MB), Italy

    Simonetta Genovesi & Andrea Stella

  2. Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

    Paola Rebora, Emanuela Rossi & Maria Grazia Valsecchi

  3. Nephrology Unit, San Gerardo Hospital, Monza, Italy

    Simonetta Genovesi & Andrea Stella

  4. Nephrology Unit, San Carlo Borromeo Hospital, Milan, Italy

    Maurizio Gallieni

  5. Nephrology Unit, Infermi Hospital, Rimini, Italy

    Fabio Badiali

  6. Nephrology Unit, S. Uboldo Hospital, Cernusco sul Naviglio, Italy

    Ferruccio Conte

  7. Nephrology Unit, S. Maria Nuova Hospital, Reggio Emilia, Italy

    Sonia Pasquali

  8. Nephrology Unit, IRCCS Multimedica, Sesto S. Giovanni, Italy

    Silvio Bertoli

  9. Nephrology Unit, Ospedali Riuniti, Bergamo, Italy

    Patrizia Ondei

  10. Nephrology Unit, S. Anna Hospital, Como, Italy

    Giuseppe Bonforte

  11. Nephrology Unit, Bassini Hospital, Cinisello, Milan, Italy

    Claudio Pozzi

  12. Nephrology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy

    Antonio Santoro

Authors
  1. Simonetta Genovesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Rebora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maurizio Gallieni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea Stella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabio Badiali
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ferruccio Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sonia Pasquali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Silvio Bertoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patrizia Ondei
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giuseppe Bonforte
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Claudio Pozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Emanuela Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Maria Grazia Valsecchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Antonio Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simonetta Genovesi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human rights

Procedures were performed according to the Helsinki declaration for ethical treatment of human subjects and approved by the local ethical committee.

Informed consent

Informed consent was obtained from the enrolled subjects.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 18 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Genovesi, S., Rebora, P., Gallieni, M. et al. Effect of oral anticoagulant therapy on mortality in end-stage renal disease patients with atrial fibrillation: a prospective study. J Nephrol 30, 573–581 (2017). https://doi.org/10.1007/s40620-016-0364-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40620-016-0364-8

Keywords

Search

Navigation