Patients who take uneven doses of acenocoumarol exhibit significant fluctuating levels of anticoagulation

Acenocoumarol is the most widely used oral anticoagulant in Spain. In clinical practice it is usual to cut 4 mg tablets into halves and quarters, so that the total weekly dose may be uniformly distributed. Nevertheless, many patients are told to take uneven doses (e.g. 1/2 tablet one day and 1/4 tablet the next day). The impact of these variations in dosage over the stability of anticoagulation is unknown. We carried out a prospective study comparing a group of 40 patients taking uneven doses of acenocoumarol and another group of 10 patients with uniform doses. All patients were within the therapeutic range at inclusion in the study. The International Normalized Ratio (INR) was determined over two consecutive days in every patient to assess possible fluctuations of anticoagulation. Patients receiving an uneven dosage showed a greater variability of the INR value over two consecutive days, as opposed to patients receiving uniform doses. Variation of the INR resulted in a dose change in 27.5% of cases with uneven dosage and in none of the uniform dose cases. Consistent association was found between every INR value and the dose administered to the patient 2 days before (P < 0.01). Patients who take uneven doses of acenocoumarol exhibit significant fluctuating levels of anticoagulation. This fact has to be considered before making any change in the acenocoumarol dose. The INR value obtained depends greatly on the dose administered 2 days before determination of the INR.