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A retrospective cohort study of the effectiveness and safety of dabigatran versus rivaroxaban in overweight patients with nonvalvular atrial fibrillation

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Abstract

Background

Guidance for dabigatran and rivaroxaban in overweight patients diagnosed with non-valvular atrial fibrillation (NVAF) is still lacking.

Aim

Compare the effectiveness and safety of dabigatran and rivaroxaban for the treatment of NVAF in the overweight population.

Method

A total of 396 out of 1029 overweight patients with NVAF at Zhongshan Hospital, Fudan University, from January 2017 and December 2018 were retrospectively enrolled using propensity score matching analysis. The clinical outcomes were analyzed by chi-square test and Kaplan–Meier analyses. The risk of bleeding and thrombosis was assessed using a Cox regression analysis and validated using a nomogram model.

Results

In terms of effectiveness, the incidence of thrombosis events and the time to thrombosis were similar in the dabigatran and rivaroxaban groups (P > 0.05). Regarding safety, compared to dabigatran, the rivaroxaban group had a higher incidence of bleeding events (8.6% vs. 3.5%, χ2 = 4.435, P = 0.035), a shorter time to bleeding (11.3 ± 0.18 months vs. 11.6 ± 0.14 months, P = 0.038) and an increased risk of bleeding (hazard ratio HR = 2.452, 95% confidence interval CI 1.017–5.913, P = 0.046), especially in those patients with heart failure (HR = 3.207, 95% CI 1.183–8.694, P = 0.022).

Conclusion

Dabigatran therapy was shown to be equally effective. It may be superior in reducing bleeding risk in an overweight population with NVAF than rivaroxaban. Further prospective studies are encouraged for analysis.

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References

  1. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962.

    Article  PubMed  Google Scholar 

  2. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the heart rhythm society in collaboration with the society of thoracic surgeons. Circulation. 2019;140:e125–51.

    Article  PubMed  Google Scholar 

  3. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139:e56–528.

    Article  PubMed  Google Scholar 

  4. Huang YL, Chen CY, Chu CC. Risk of major bleeding and thromboembolism in Asian patients with nonvalvular atrial fibrillation using direct oral anticoagulants versus warfarin. Int J Clin Pharm. 2022;44(1):34–43.

    Article  CAS  PubMed  Google Scholar 

  5. Burnett AE, Mahan CE, Vazquez SR, et al. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;4:206–32.

    Article  Google Scholar 

  6. Mourad AP, Aslani P, D’Souza M, et al. The acceptability of a direct oral anticoagulant monitoring regimen among patients with atrial fibrillation: a pilot study. Int J Clin Pharm. 2019;41(3):682–6.

    Article  CAS  PubMed  Google Scholar 

  7. Tedrow UB, Conen D, Ridker PM, et al. The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation the WHS (women’s health study). J Am Coll Cardiol. 2010;55:2319–27.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Aune D, Sen A, Schlesinger S, et al. Body mass index, abdominal fatness, fat mass and the risk of atrial fibrillation: a systematic review and dose-response meta-analysis of prospective studies. Eur J Epidemiol. 2017;32:181–92.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sivasambu B, Balouch MA, Zghaib T, et al. Increased rates of atrial fibrillation recurrence following pulmonary vein isolation in overweight and obese patients. J Cardiovasc Electrophysiol. 2018;29:239–45.

    Article  PubMed  Google Scholar 

  10. Breuer L, Ringwald J, Schwab S, et al. Ischemic stroke in an obese patient receiving dabigatran. N Engl J Med. 2013;368:2440–2.

    Article  CAS  PubMed  Google Scholar 

  11. Lucijanic M, Jurin I, Jurin H, et al. Patients with higher body mass index treated with direct/novel oral anticoagulants (DOAC/NOAC) for atrial fibrillation experience worse clinical outcomes. Int J Cardiol. 2020;301:90–5.

    Article  PubMed  Google Scholar 

  12. Safouris A, Demulder A, Triantafyllou N, et al. Rivaroxaban presents a better pharmacokinetic profile than dabigatran in an obese non-diabetic stroke patient. J Neurol Sci. 2014;346:366–7.

    Article  CAS  PubMed  Google Scholar 

  13. Li X, Zuo C, Ji Q, et al. Body mass index influence on the clinical outcomes for nonvalvular atrial fibrillation patients admitted to a hospital treated with direct oral anticoagulants: a retrospective cohort study. Drug Des Devel Ther. 2021;15:1931–43.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kaplan RM, Tanaka Y, Passman RS, et al. Efficacy and safety of direct oral anticoagulants for atrial fibrillation across body mass index categories. J Am Heart Assoc. 2020;9:e017383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Uprichard J. Management of rivaroxaban in relation to bodyweight and body mass index. Ther Adv Cardiovasc Dis. 2016;10:294–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kido K, Ngorsuraches S. Comparing the efficacy and safety of direct oral anticoagulants with warfarin in the morbidly obese population with atrial fibrillation. Ann Pharmacother. 2019;53(02):165–70.

    Article  CAS  PubMed  Google Scholar 

  17. Abildgaard A, Madsen SA, Hvas AM. Dosage of anticoagulants in obesity: recommendations based on a systematic review. Semin Thromb Hemost. 2020;46(8):932–69.

    Article  PubMed  Google Scholar 

  18. Adeboyeje G, Sylwestrzak G, Barron JJ, et al. Major bleeding risk during anticoagulation with warfarin, dabigatran, apixaban, or rivaroxaban in patients with nonvalvular atrial fibrillation. J Manag Care Spec Pharm. 2017;23:968–78.

    PubMed  Google Scholar 

  19. Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49:71–87.

    Article  CAS  PubMed  Google Scholar 

  20. Mocini D, Di Fusco SA, Mocini E, et al. Direct oral anticoagulants in patients with obesity and atrial fibrillation: position paper of Italian National Association of Hospital Cardiologists (ANMCO). J Clin Med. 2021;10:4185. Accessed 15 Jul 2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Martin KA, Beyer-Westendorf J, Davidson BL, et al. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost. 2021;19:1874–82.

    Article  PubMed  Google Scholar 

  22. WHOE Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.

    Article  Google Scholar 

  23. Guler E, Babur Guler G, Demir GG, et al. A review of the fixed dose use of new oral anticoagulants in obese patients: Is it really enough? Anatol J Cardiol. 2015;15:1020–9.

    Article  CAS  PubMed  Google Scholar 

  24. Guyatt GH, Norris SL, Schulman S, et al. Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:53S-70S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Spyropoulos AC, Brohi K, Caprini J, et al. Scientific and Standardization Committee Communication: guidance document on the periprocedural management of patients on chronic oral anticoagulant therapy: recommendations for standardized reporting of procedural/surgical bleed risk and patient-specific thromboembolic risk. J Thromb Haemost. 2019;17:1966–72.

    Article  PubMed  Google Scholar 

  26. Kim D, Yang PS, Jang E, et al. Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation. Europace. 2021;23:184–95.

    Article  PubMed  Google Scholar 

  27. Lip GYH, Keshishian A, Kang A, et al. Effectiveness and safety of oral anticoagulants among non-valvular atrial fibrillation patients with polypharmacy. Eur Heart J Cardiovasc Pharmacother. 2021;7:405–14.

    Article  PubMed  Google Scholar 

  28. Peng B, Min R, Liao Y, et al. Development of predictive nomograms for clinical use to quantify the risk of amputation in patients with diabetic foot ulcer. J Diabetes Res. 2021;2021:6621035.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Yang E. A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation–full speed ahead or proceed with caution? Vasc Health Risk Manag. 2014;10:507–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lopez-Lopez JA, Sterne JAC, Thom HHZ, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017;359:j5058.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhou Y, Ma J, Zhu W. Efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation across BMI categories: a systematic review and meta-analysis. Am J Cardiovasc Drugs. 2020;20:51–60.

    Article  PubMed  Google Scholar 

  32. Piran S, Traquair H, Chan N, et al. Peak plasma concentration of direct oral anticoagulants in obese patients weighing over 120 kilograms: a retrospective study. Res Pract Thromb Haemost. 2018;2:684–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Martin K, Beyer-Westendorf J, Davidson BL, et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14:1308–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Alma LJ, De Groot CJM, De Menezes RX, et al. Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: high BMI is key. Eur J Obstet Gynecol Reprod Biol. 2018;225:62–9.

    Article  CAS  PubMed  Google Scholar 

  35. Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral anticoagulants: risk, prevention and management. World J Gastroenterol. 2017;23:1954–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY trial (randomized evaluation of long-term anticoagulation therapy). J Am Coll Cardiol. 2014;63:321–8.

    Article  CAS  PubMed  Google Scholar 

  37. Piccini JP, Stevens SR, Chang Y, et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts. Circulation. 2013;127:224–32.

    Article  CAS  PubMed  Google Scholar 

  38. Apostolakis S, Lane DA, Banerjee A. Letter by Apostolakis et al regarding article, “renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R2CHADS2 index in the ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study cohorts.” Circulation. 2013;128:e171.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank the medical staff and patients who contributed to this research.

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Correspondence to Xiaoye Li or Qianzhou Lv.

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Yu, M., Wang, Z., Zong, L. et al. A retrospective cohort study of the effectiveness and safety of dabigatran versus rivaroxaban in overweight patients with nonvalvular atrial fibrillation. Int J Clin Pharm 44, 1149–1157 (2022). https://doi.org/10.1007/s11096-022-01443-2

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  • DOI: https://doi.org/10.1007/s11096-022-01443-2

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