European Journal of Clinical Pharmacology

, Volume 70, Issue 9, pp 1049–1057

Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study

  • Jean-Philippe Collet
  • Jean-Sébastien Hulot
  • Jérémie Abtan
  • Ghalia Anzaha
  • Mathieu Kerneis
  • Johanne Silvain
  • Guillaume Cayla
  • Stephen A. O’Connor
  • Olivier Barthélémy
  • Farzin Beygui
  • Sophie Galier
  • Delphine Brugier
  • Eric J. Stanek
  • Scott L. Charland
  • Vanessa Gallois
  • Gilles Montalescot
  • for the DOSAPI investigators.
Clinical Trial

DOI: 10.1007/s00228-014-1710-1

Cite this article as:
Collet, J., Hulot, J., Abtan, J. et al. Eur J Clin Pharmacol (2014) 70: 1049. doi:10.1007/s00228-014-1710-1

Abstract

Aims

The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction.

Method and results

In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline].

The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (−53.6±48.4 % versus +0.8±53.7 % without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (−81.8 %±24.8 % vs. −72.9 %±32.9 % without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups.

Conclusion

The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

Keywords

ThienopyridineProton pump inhibitorPlatelet reactivityCoronary artery disease

Supplementary material

228_2014_1710_MOESM1_ESM.odt (8 kb)
ESM 1(ODT 7 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jean-Philippe Collet
    • 1
  • Jean-Sébastien Hulot
    • 2
    • 3
  • Jérémie Abtan
    • 1
  • Ghalia Anzaha
    • 1
  • Mathieu Kerneis
    • 1
  • Johanne Silvain
    • 1
  • Guillaume Cayla
    • 1
  • Stephen A. O’Connor
    • 1
  • Olivier Barthélémy
    • 1
  • Farzin Beygui
    • 1
  • Sophie Galier
    • 1
  • Delphine Brugier
    • 1
  • Eric J. Stanek
    • 4
  • Scott L. Charland
    • 4
  • Vanessa Gallois
    • 1
  • Gilles Montalescot
    • 1
    • 5
  • for the DOSAPI investigators.
  1. 1.ACTION Study Group, Hôpital Pitié-Salpêtrière (APHP), Institut de Cardiologie, INSERM, UMR_S 1166, Pitié-Salpêtrière Hospital (AP-HP)Université Pierre et Marie Curie (UPMC Paris 6)ParisFrance
  2. 2.UPMC Univ Paris 06, UMR_S 1166, ICANSorbonne UniversitésParisFrance
  3. 3.Department of Pharmacology & Institute of CardioMetabolism and NutritionAP-HP, Hôpital Pitié-SalpêtrièreParisFrance
  4. 4.Medco Research InstituteMedco Health Solutions, Inc.Franklin LakesUSA
  5. 5.Institut de Cardiologie, Bureau 2-236Pitié-Salpêtrière University HospitalParisFrance