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

The effect of concomitantly administered clopidogrel on anti-coagulation 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.