Skip to main content

Advertisement

SpringerLink
Log in

Associated factors and safety of the rapidly achieving first therapeutic target of warfarin in hospitalized patients: a retrospective cohort study

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background

Warfarin is a commonly used anticoagulant drug in clinical practice. Rapidly achieving the first therapeutic international normalized ratio (INR) of warfarin may reduce the hospital length of stay. However, little research has been carried out to evaluate the influencing factors and the safety of rapidly achieving the first therapeutic INR target of warfarin.

Aim

To investigate the associated factors and the safety of rapidly achieving the first therapeutic INR target of warfarin.

Method

A retrospective cohort study was conducted in inpatients who took warfarin from November 2018 to October 2019. Patients’ information was retrieved from medical records.

Results

487 patients were included. The mean achieving first therapeutic target time was 6.0 ± 3.2 days (median, 5.0 days). Age > 65 years, body mass index < 24 kg/m2, and initial warfarin dose ≥ 3 mg/d were independent factors associated with the rapidly achieving first INR target of warfarin therapy. The incidence of INR ≥ 4 was higher in patients achieving the first INR target rapidly than those achieving the first INR target slowly, while there were no significant differences in bleeding events between the two groups.

Conclusion

Hospitalized patients aged > 65 years, with a body mass index < 24 kg/m2, or receiving an initial warfarin dose ≥ 3 mg/d were more likely to achieve the first INR target of warfarin rapidly. Closer INR monitoring and appropriate warfarin dose adjustment are recommended to improve the safety for patients achieving the first INR ≥ 1.8 within 6 days after beginning oral warfarin.

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. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl): e44S-e88S.

  2. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315–52.

    Article  Google Scholar 

  3. Xu Z, Zhang SY, Huang M, et al. Genotype-Guided Warfarin Dosing in Patients with Mechanical Valves: A Randomized Controlled Trial. Ann Thorac Surg. 2018;106(6):1774–81.

    Article  Google Scholar 

  4. Lu Y, Yang J, Zhang H, et al. Prediction of warfarin maintenance dose in Han Chinese patients using a mechanistic model based on genetic and non-genetic factors. Clin Pharmacokinet. 2013;52(7):567–81.

    Article  CAS  Google Scholar 

  5. Godoy LC, Tomlinson G, Abumuamar AM, et al. Association between time to therapeutic INR and length of stay following mechanical heart valve surgery. J Card Surg. 2022;37(1):62–9.

    Article  Google Scholar 

  6. Pastori D, Pignatelli P, Cribari F, et al. Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists-naive patients with atrial fibrillation. Am Heart J. 2018;200:32–6.

    Article  CAS  Google Scholar 

  7. Arendt CJ, Hong JH, Daly RC, et al. Time to achieving therapeutic international normalized ratio increases hospital length of stay after heart valve replacement surgery. Am Heart J. 2017;187:70–7.

    Article  Google Scholar 

  8. Dentali F, Pignatelli P, Malato A, et al. Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: a prospective multicenter cohort study. Am J Hematol. 2012;87(4):384–7.

    Article  Google Scholar 

  9. Wallace JL, Reaves AB, Tolley EA, et al. Comparison of initial warfarin response in obese patients versus non-obese patients. J Thromb Thrombolysis. 2013;36(1):96–101.

    Article  CAS  Google Scholar 

  10. Liu J, Guan H, Zhou L, et al. Impact of gene polymorphism on the initiation and maintenance phases of warfarin therapy in Chinese patients undergoing heart valve replacement. Am J Transl Res. 2019;11(4):2507–15.

    CAS  Google Scholar 

  11. Acar T, Aras YG, Gül SS, et al. Effective INR Level May Be Delayed in Secondary Prevention of Stroke Due to Atrial Fibrillation with Warfarin in the Patients with Diabetes Mellitus. Noro Psikiyatr Ars. 2018;56(4):273–6.

    Google Scholar 

  12. Naik DS, Pillai VM, Adole PS. Comparison of 10-mg and 5-mg warfarin initiation nomograms in a South Indian population - An open label trial. Thromb Res. 2019;176:33–5.

    Article  Google Scholar 

  13. Farahmand S, Saeedi M, Seyed Javadi HH, et al. High doses of warfarin are more beneficial than its low doses in patients with deep vein thrombosis. Am J Emerg Med. 2011;29(9):1222–6.

    Article  Google Scholar 

  14. Temple R. Hy’s law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Saf. 2006;15(4):241–3.

    Article  Google Scholar 

  15. Xu H, Cai H, Qian Z, et al. Dosing practice of low molecular weight heparins and its efficacy and safety in cardiovascular inpatients: a retrospective study in a Chinese teaching hospital. BMC Cardiovasc Disord. 2012;12:118.

    Article  CAS  Google Scholar 

  16. Schulman S, Angerås U, Bergqvist D, et al. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8(1):202–4.

    Article  CAS  Google Scholar 

  17. Bahit MC, Lopes RD, Wojdyla DM, et al. Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation. Heart. 2017;103(8):623–8.

    Article  CAS  Google Scholar 

  18. Pirmohamed M, Burnside G, Eriksson N, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369(24):2294–303.

    Article  CAS  Google Scholar 

  19. Wen MS, Chang KC, Lee TH, et al. Pharmacogenetic dosing of warfarin in the Han-Chinese population: a randomized trial. Pharmacogenomics. 2017;18(3):245–53.

    Article  CAS  Google Scholar 

  20. Jin H, Jiang F, Wei J, et al. CYP2C9 and VKORC1 genotype-guided individualized warfarin therapy in Chinese patients with acute pulmonary thromboembolism: a randomized controlled clinical study. Int J Clin Exp Med. 2017;10(3):5595–602.

    CAS  Google Scholar 

  21. Lip GYH, Al-Saady N, Jin J, et al. Anticoagulation Control in Warfarin-Treated Patients Undergoing Cardioversion of Atrial Fibrillation (from the Edoxaban Versus Enoxaparin-Warfarin in Patients Undergoing Cardioversion of Atrial Fibrillation Trial). Am J Cardiol. 2017;120(5):792–6.

    Article  CAS  Google Scholar 

  22. Moffett BS, Bomgaars LR. Response to warfarin therapy in obese pediatric patients dosed according to institutional guidelines. J Pediatr Hematol Oncol. 2014;36(8):e487–9.

    Article  Google Scholar 

  23. Shendre A, Parmar GM, Dillon C, et al. Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacotherapy. 2018;38(6):588–96.

    Article  CAS  Google Scholar 

  24. Hu DY, Sun YH. Chinese Expert Consensus of warfarin anticoagulant therapy. Zhonghua nei ke za zhi. 2013;52(1):76–82. (In Chinese).

    Google Scholar 

  25. Ning X, Kuang Y, Yang G, et al. Influence of renal insufficiency on anticoagulant effects and safety of warfarin in Chinese patients: analysis from a randomized controlled trial. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(6):1275–83.

    Article  CAS  Google Scholar 

  26. Suwanawiboon B, Kongtim P, Chinthammitr Y, et al. The efficacy of 3-mg warfarin initiating dose in adult Thai patients, who required long-term anticoagulant therapy. J Med Assoc Thai. 2011;94(Suppl 1):225–31.

    Google Scholar 

  27. Li B, Liu R, Wang C, et al. Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery. Eur J Clin Pharmacol. 2019;75(12):1685–93.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China

    Wenjun Yang, Wei Hu, Haibin Dai & Huimin Xu

  2. College of Pharmacy, Hangzhou Medical College, 310053, Hangzhou, China

    Jun Ma

Authors
  1. Wenjun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haibin Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huimin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huimin Xu.

Ethics declarations

Conflicts of interest

The authors have no conflicts of interest to declare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, W., Ma, J., Hu, W. et al. Associated factors and safety of the rapidly achieving first therapeutic target of warfarin in hospitalized patients: a retrospective cohort study. Int J Clin Pharm 44, 939–946 (2022). https://doi.org/10.1007/s11096-022-01404-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-022-01404-9

Keywords

Search

Navigation