Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation
Christer Lidell1, Lars-Erik Svedberg2, Peter Lindell3, Stellan Bandh4, Bernhard Job5, Lars Wallentin1
1Department of Cardiology, Uppsala University Hospital, 2Department of Medicine, Bollnäs Hospital, 3Department of Cardiology, Huddinge Hospital, 4Department of Cardiology, Västeras Hospital, Sweden, 5Sanofi-Synthélabo Recherche, Chilly-Mazarin, France
Summary The effect of concomitantly administered clopidogrel on anticoagulationstatus was investigated in patients receiving longtermwarfarin therapy. Forty-three patients with non-valvularatrial fibrillation who were receiving long-term warfarin andhad a stable international normalized ratio (INR) between 2and 3 were randomly assigned to clopidogrel 75 mg daily orplacebo for 8 days (Days 1-8). INR (primary endpoint) andplasma 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 percentagechange from baseline being 0.6% at Day 6. Plasmalevels of R- and S-warfarin also remained very stable in thosereceiving clopidogrel. No serious adverse events, prematurediscontinuations of study drug or bleeding occurred with clopidogrel.In conclusion, the stable anticoagulation status ofpatients receiving long-term warfarin therapy is unaffected byconcomitant administration of clopidogrel 75 mg daily.