Download PDF
Thromb Haemost 2003; 89(05): 842-846
DOI: 10.1055/s-0037-1613471
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation

Christer Lidell
1   Department of Cardiology, Uppsala University Hospital, Sweden
,
Lars-Erik Svedberg
2   Department of Medicine, Bollnäs Hospital, Sweden
,
Peter Lindell
3   Department of Cardiology, Huddinge Hospital, Sweden
,
Stellan Bandh
4   Department of Cardiology, Västeras Hospital, Sweden
,
Bernhard Job
5   Sanofi-Synthélabo Recherche, Chilly-Mazarin, France
,
Lars Wallentin
1   Department of Cardiology, Uppsala University Hospital, Sweden
› Author Affiliations
Further Information

Publication History

Received 05 September 2002

Accepted after revision 04 February 2003

Publication Date:
09 December 2017 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

The effect of concomitantly administered clopidogrel on anticoagulation status was investigated in patients receiving long-term warfarin therapy. Forty-three patients with non-valvular atrial fibrillation who were receiving long-term warfarin and had a stable international normalized ratio (INR) between 2 and 3 were randomly assigned to clopidogrel 75 mg daily or placebo for 8 days (Days 1–8). INR (primary endpoint) and plasma levels of warfarin enantiomers (secondary endpoint) were evaluated at Days 3, 6, 9, 13 and 22. Mean INR remained extremely stable in the clopidogrel group, the maximum percentage change from baseline being 0.6% at Day 6. Plasma levels of R- and S-warfarin also remained very stable in those receiving clopidogrel. No serious adverse events, premature discontinuations of study drug or bleeding occurred with clopidogrel. In conclusion, the stable anticoagulation status of patients receiving long-term warfarin therapy is unaffected by concomitant administration of clopidogrel 75 mg daily.

Keywords

Clopidogrel - drug interaction - warfarin
 

  • References

  • 1 Kannel WB.. et al. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med 1982; 306: 1018-22.
    CrossrefPubMedSearch in Google Scholar
  • 2 Bialy D, Lehmann L, Schumacher DN.. et al. Hospitalisation for arrhythmias in the United States: importance of atrial fibrillation. J Am Coll Cardiol 1992; 19: 41A.
    PubMedSearch in Google Scholar
  • 3 Benjamin EJ.. et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998; 98: 946-952.
    CrossrefPubMedSearch in Google Scholar
  • 4 Ryder KM, Benjamin EJ.. Epidemiology and significance of atrial fibrillation. Am J Cardiol 1999; 84: 131R-8R.
    CrossrefPubMedSearch in Google Scholar
  • 5 Wolf PA, Abbott RD, Kannel WB.. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-8.
    CrossrefPubMedSearch in Google Scholar
  • 6 Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized trials. Arch Intern Med 1994; 154: 1449-57.
    CrossrefPubMedSearch in Google Scholar
  • 7 Cleland JGF, Cowburn PJ, Falk RH.. Should all patients with atrial fibrillation receive warfarin?. Eur Heart J 1996; 17: 674-681.
    CrossrefPubMedSearch in Google Scholar
  • 8 Albers GW.. et al. Antithrombotic therapy in atrial fibrillation. Chest 2001; 119 (Suppl. 01) (Suppl) 194S-206S.
    CrossrefPubMedSearch in Google Scholar
  • 9 CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329-39.
    CrossrefPubMedSearch in Google Scholar
  • 10 Yusuf S, Zhao F, Mehta SR.. et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502.
    CrossrefPubMedSearch in Google Scholar
  • 11 Mehta SR, Yusuf S, Peters RJ.. et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527-33.
    CrossrefPubMedSearch in Google Scholar
  • 12 Bertrand ME, Simoons ML, Fox KA, Wallentin LC, Hamm CW, McFadden E, De Feyter PJ, Specchia G, Ruzyllo W.. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002; 23: 1809-40.
    CrossrefPubMedSearch in Google Scholar
  • 13 Savi P, Combalbert J, Gaich C.. et al. The anti-aggregating activity of clopidogrel is due to a metabolic activation by the hepatic cyto-chrome P450-1A. Thromb Haemost 1994; 72: 313-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Guillin MC, Bonnet G, Sissmann J, Necciari J, Dickinson JP.. Pharmacodynamics and pharmacokinetics of the novel antiplatelet agent, clopidogrel, in the young and the elderly with and without symptomatic atherosclerosis. Eur Heart J 1996; 17 (Suppl) 161.
    PubMedSearch in Google Scholar
  • 15 Herbert JM.. et al. Clopidogrel, a novel antiplatelet and atherothrombotic agent. Cardiovasc Drug Rev 1993; 11: 180-98.
    CrossrefPubMedSearch in Google Scholar
  • 16 Thebault J-J, Kieffer G, Lowe GDO, Nimmo WS, Cariou R.. Repeated-dose pharmacodynamics of clopidogrel in healthy subjects. Semin Thromb Hemost 1999; 25 (Suppl. 02) (Suppl) 9-14.
    PubMedSearch in Google Scholar
  • 17 Morais J.. Use of concomitant medications in the CAPRIE trial: clopidogrel is unlikely to be associated with clinically significant drug interactions. Eur Heart J 1998; 19: 5.
    PubMedSearch in Google Scholar