Length of hospitalization and mortality for bleeding during treatment with warfarin, dabigatran, or rivaroxaban

Blake Charlton, Gboyega Adeboyeje, John J Barron, Deborah Grady, Jaekyu Shin, Rita F Redberg, Blake Charlton, Gboyega Adeboyeje, John J Barron, Deborah Grady, Jaekyu Shin, Rita F Redberg

Abstract

Background: Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban.

Methods: An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality.

Results: Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8-2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9-3.9; p < 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality.

Conclusions: Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin.

Conflict of interest statement

Competing Interests: Gboyega Adeboyeje and John J Barron were employed by HealthCore, a wholly-owned and independently operated subsidiary of Anthem, Inc. There are no conflicts of interests for any of the authors. The affiliation with HealthCore does not alter our adherence to PLOS ONE policies.

Figures

Fig 1. Cohort definition.
Fig 1. Cohort definition.
Fig 2. Differences in adjusted mean total…
Fig 2. Differences in adjusted mean total length of stay.

References

    1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009. September 17;361(12):1139–51. doi:
    1. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011. September 8;365(10):883–91. doi:
    1. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011. September 15;365(11):981–92. doi:
    1. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013. November 28;369(22):2093–104. doi:
    1. Adam SS, McDuffie JR, Ortel TL, Williams JW. Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review. Ann Intern Med. 2012. December 4;157(11):796–807. doi:
    1. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014. March 15;383(9921):955–62. doi:
    1. Sherwood MW, Nessel CC, Hellkamp AS, Mahaffey KW, Piccini JP, Suh E-Y, et al. Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial. J Am Coll Cardiol. 2015. December 1;66(21):2271–81. doi:
    1. Skaistis J, Tagami T. Risk of Fatal Bleeding in Episodes of Major Bleeding with New Oral Anticoagulants and Vitamin K Antagonists: A Systematic Review and Meta-Analysis. PloS One. 2015;10(9):e0137444 doi:
    1. Saji N, Kimura K, Aoki J, Uemura J, Sakamoto Y. Intracranial Hemorrhage Caused by Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)- Multicenter Retrospective Cohort Study in Japan. Circ J Off J Jpn Circ Soc. 2015;79(5):1018–23.
    1. Hagii J, Tomita H, Metoki N, Saito S, Shiroto H, Hitomi H, et al. Characteristics of intracerebral hemorrhage during rivaroxaban treatment: comparison with those during warfarin. Stroke J Cereb Circ. 2014. September;45(9):2805–7.
    1. Details | Assessments of Health Outcomes Among Individuals Exposed to Medical Products | Mini-Sentinel [Internet]. [cited 2015 Nov 9]. Available from:
    1. Wahl PM, Rodgers K, Schneeweiss S, Gage BF, Butler J, Wilmer C, et al. Validation of claims-based diagnostic and procedure codes for cardiovascular and gastrointestinal serious adverse events in a commercially-insured population. Pharmacoepidemiol Drug Saf. 2010. June 1;19(6):596–603. doi:
    1. Singer DE, Chang Y, Borowsky LH, Fang MC, Pomernacki NK, Udaltsova N, et al. A new risk scheme to predict ischemic stroke and other thromboembolism in atrial fibrillation: the ATRIA study stroke risk score. J Am Heart Assoc. 2013. June;2(3):e000250 doi:
    1. Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? JAMA. 2003. November 26;290(20):2685–92. doi:
    1. Dahl OE, Kurth AA, Rosencher N, Noack H, Clemens A, Eriksson BI. Thromboprophylaxis in patients older than 75 years or with moderate renal impairment undergoing knee or hip replacement surgery [corrected]. Int Orthop. 2012. April;36(4):741–8. doi:
    1. Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf. 2011. June;20(6):560–6. doi:
    1. Rubin DB, Thomas N. Matching using estimated propensity scores: relating theory to practice. Biometrics. 1996. March;52(1):249–64.
    1. Spreeuwenberg MD, Bartak A, Croon MA, Hagenaars JA, Busschbach JJV, Andrea H, et al. The multiple propensity score as control for bias in the comparison of more than two treatment arms: an introduction from a case study in mental health. Med Care. 2010. February;48(2):166–74. doi:
    1. Imbens GW. The role of the propensity score in estimating dose-response functions. Biometrika. 2000. September 1;87(3):706–10.
    1. Glynn RJ, Schneeweiss S, Stürmer T. Indications for propensity scores and review of their use in pharmacoepidemiology. Basic Clin Pharmacol Toxicol. 2006. March;98(3):253–9. doi:
    1. Stürmer T, Joshi M, Glynn RJ, Avorn J, Rothman KJ, Schneeweiss S. A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods. J Clin Epidemiol. 2006. May;59(5):437–47. doi:
    1. Cadarette SM, Katz JN, Brookhart MA, Stürmer T, Stedman MR, Solomon DH. Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture. Ann Intern Med. 2008. May 6;148(9):637–46.
    1. Ashburner JM, Go AS, Reynolds K, Chang Y, Fang MC, Fredman L, et al. Comparison of frequency and outcome of major gastrointestinal hemorrhage in patients with atrial fibrillation on versus not receiving warfarin therapy (from the ATRIA and ATRIA-CVRN cohorts). Am J Cardiol. 2015. January 1;115(1):40–6. doi:
    1. Beyer-Westendorf J, Förster K, Pannach S, Ebertz F, Gelbricht V, Thieme C, et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood. 2014. August 7;124(6):955–62. doi:
    1. Fang MC, Go AS, Chang Y, Hylek EM, Henault LE, Jensvold NG, et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med. 2007. August;120(8):700–5. doi:
    1. Halbritter K, Beyer-Westendorf J, Nowotny J, Pannach S, Kuhlisch E, Schellong SM. Hospitalization for vitamin-K-antagonist-related bleeding: treatment patterns and outcome. J Thromb Haemost JTH. 2013. April;11(4):651–9. doi:
    1. Gheorghiade M, Vaduganathan M, Fonarow GC, Bonow RO. Rehospitalization for heart failure: problems and perspectives. J Am Coll Cardiol. 2013. January 29;61(4):391–403. doi:
    1. Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015. November 11;
    1. Majeed A, Hwang H-G, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013. November 19;128(21):2325–32. doi:
    1. Piccini JP, Garg J, Patel MR, Lokhnygina Y, Goodman SG, Becker RC, et al. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial. Eur Heart J. 2014. July 21;35(28):1873–80. doi:
    1. Held C, Hylek EM, Alexander JH, Hanna M, Lopes RD, Wojdyla DM, et al. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur Heart J. 2015. May 21;36(20):1264–72. doi:
    1. da Graca B, Filardo G, Nicewander D. Consequences for healthcare quality and research of the exclusion of records from the Death Master File. Circ Cardiovasc Qual Outcomes. 2013. January 1;6(1):124–8. doi:

Source: PubMed

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