Patients with an ApoE ε4 allele require lower doses of coumarin anticoagulants

Objective: Vitamin K is an essential cofactor for the synthesis of several blood coagulation factors. It has been suggested that the apolipoprotein E (ApoE) genotype has profound effects on vitamin K status. Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of coumarin anticoagulants. Methods: We did a cohort study in 1637 patients from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon. Results: To attain the same level of anticoagulation, patients with genotype ε4/ε4 and genotype ε3/ε4 required respectively 3.4 mg (95%CI: -6.0 to -0.9) and 0.8 mg (95%CI: -1.6 to 0.1) acenocoumarol per week less than patients with genotype ε3/ε3. Patients homozygous for the ε2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more than patients with genotype ε3/ε3. The acenocoumarol maintenance dose showed a gene dose effect of the ε4 allele, but not of the ε2 allele. No significant dose difference was observed for phenprocoumon, possibly because of low numbers. Conclusion: The ApoE genotype affects the dose requirements of acenocoumarol.