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Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study

  • Tomáš Bolek
  • Matej Samoš
  • Ingrid Škorňová
  • Lucia Stančiaková
  • Ján Staško
  • Barbora Korpallová
  • Peter Galajda
  • Peter Kubisz
  • Marián Mokáň
Article
  • 55 Downloads

Abstract

Proton pump inhibition (PPI) reduces gastrointestinal bleeding on direct oral anticoagulants. However, PPI may affect dabigatran on-treatment levels; and there is no information regarding the effect of PPI on xabans on-treatment activity. Thus, the aim of this study was to determine the impact of PPI on therapeutic anti-Xa activity in rivaroxaban- and apixaban-treated patients with atrial fibrillation (AF). This single-centre pilot prospective study enrolled 77 consecutive xabans-treated patients (42 rivaroxaban-treated and 35 apixaban-treated patients) with AF. PPI was administrated in 44 patients. Trough and peak anti-Xa activity was assessed with factor Xa-calibrated anti-Xa chromogenic analysis. There were no significant differences in trough anti-Xa activity comparing PPI-treated patients and patients without PPI (80.5 ± 66.5 ng/mL in PPI group vs. 71.6 ± 64.1 ng/mL in non-PPI group, p = 0.57, Table 2). Similarly, there were no significant differences in peak anti-Xa activity between compared groups (175.2 ± 102.5 ng/mL in PPI group vs. 202.9 ± 84.1 ng/mL in non-PPI group, p = 0.21). This pilot study did not reveal significant changes in xabans on-treatment anti-Xa activity according the PPI status.

Keywords

Proton pump inhibitors Xabans Rivaroxaban Apixaban Anti-Xa activity Atrial fibrillation 

Notes

Acknowledgements

This study was supported by Research Project of Comenius University in Bratislava UK/386/2018 and by Research Project APVV (Slovak Research and Development Agency) 16-0020.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethical approval

This research was done according to ethical standards and was approved by the Local Ethical Committee (Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava).

Informed consent

The patients agreed to participate in the research and signed informed consent for study participation.

References

  1. 1.
    He Y, Wong IC, Li X et al (2016) The association between non-vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta-analysis of observational studies. Br J Clin Pharmacol 82:285–300CrossRefGoogle Scholar
  2. 2.
    Bolek T, Samoš M, Stančiaková L, Ivanková J, Škorňová I, Staško J, Galajda P, Kubisz P, Mokáň M (2017) The Impact of proton pump inhibition on dabigatran levels in patients with atrial fibrillation. Am J Ther.  https://doi.org/10.1097/MJT.0000000000000599 CrossRefPubMedGoogle Scholar
  3. 3.
    Bayer AG (2017) Xarelto® (rivaroxaban) summary of product characteristics. Bayer AG, WhippanyGoogle Scholar
  4. 4.
    Bristol-Myers Squibb/Pfizer EEIG (2017) Eliquis® (apixaban) summary of product characteristics. Bristol-Myers Squibb/Pfizer EEIG, New YorkGoogle Scholar
  5. 5.
    Mueck W, Stampfuss J, Kubitza D et al (2014) Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet 53:1–16CrossRefGoogle Scholar
  6. 6.
    Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, Pinto D, Chen S, Bonacorsi S, Wong PC, Zhang D (2009) Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos 37:74–81CrossRefGoogle Scholar
  7. 7.
    Meyer UA (1996) Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs. Eur J Gastroenterol Hepatol 8(Suppl 1):S21–S25CrossRefGoogle Scholar
  8. 8.
    Blume H, Donath F, Warnke A, Schug BS (2006) Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf 29:769–784CrossRefGoogle Scholar
  9. 9.
    Douxfils J, Tamigniau A, Chatelain B, Chatelain C, Wallemacq P, Dogné JM, Mullier F (2013) Comparison of calibrated chromogenic anti-Xa assay and PT tests with LC–MS/MS for the therapeutic monitoring of patients treated with rivaroxaban. Thromb Haemost 110:723–731CrossRefGoogle Scholar
  10. 10.
    Schmitz EM, Boonen K, van den Heuvel DJ, van Dongen JL, Schellings MW, Emmen JM, van der Graaf F, Brunsveld L, van de Kerkhof D (2014) Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants. J Thromb Haemost 12:1636–1646CrossRefGoogle Scholar
  11. 11.
    Abraham NS, Singh S, Alexander GC et al (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:h1857CrossRefGoogle Scholar
  12. 12.
    Reilly PA, Lehr T, Haertter S, RE-LY Investigators et al (2014) 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 63:321–328CrossRefGoogle Scholar
  13. 13.
    Moore KT, Plotnikov AN, Thyssen A et al (2011) Effect of multiple doses of omeprazole on the pharmacokinetics, pharmacodynamics, and safety of a single dose of rivaroxaban. J Cardiovasc Pharmacol 58:581–588CrossRefGoogle Scholar
  14. 14.
    Patel MR, Mahaffey KW, Garg J, ROCKET AF Investigators et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891CrossRefGoogle Scholar
  15. 15.
    Upreti VV, Song Y, Wang J et al (2013) Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Clin Pharmacol Adv Appl 11:59–66Google Scholar
  16. 16.
    Granger CB, Alexander JH, McMurray JJ ARISTOTLE Committees and Investigators et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992CrossRefGoogle Scholar
  17. 17.
    Sakaguchi T, Osanai H, Murase Y et al (2017) Monitoring of anti-Xa activity and factors related to bleeding events: a study in Japanese patients with nonvalvular atrial fibrillation receiving rivaroxaban. J Cardiol 70:244–249CrossRefGoogle Scholar
  18. 18.
    Testa S, Paoletti O, Legnani C et al (2018) Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost 16:842–848CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine I, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  2. 2.National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia

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