Key result
VKORC1 and CYP2C9 genotypes significantly increased the risk of over-anticoagulation (INR >2.5) (p<0.001 and p=0.002), while CYP4F2 T carriers had a lower risk (p=0.009).
Why the study?
Do VKORC1, CYP2C9 and CYP4F2 genetic variants affect early outcomes such as time to stable dosage and over-anticoagulation in patients starting acenocoumarol therapy?
Cohort (n=941)
Do VKORC1, CYP2C9 and CYP4F2 genetic variants affect early outcomes such as time to stable dosage and over-anticoagulation in patients starting acenocoumarol therapy?
VKORC1, CYP2C9, and CYP4F2 genetic variants significantly influence the time to stable dosage and risk of over-anticoagulation during the first weeks of acenocoumarol therapy.
VKORC1 AA may enable faster acenocoumarol stabilization; hypothesis-generating and requires prospective trials before any clinical adoption.
AIM: To analyze VKORC1, CYP2C9 and CYP4F2 polymorphisms in relation to the main outcomes in the first stages of acenocoumarol therapy. PATIENTS & METHODS: Nine hundred and forty one patients who had started therapy and in whom time to stable dosage, time to over-anticoagulation and adverse events occurred during 3 first months were retrospectively analyzed. RESULTS: VKORC1 AA patients needed fewer days to reach stable dosage (p = 0.017). International normalized ratio [INR] at 72 h, and VKORC1 and CYP2C9 genotypes conditioned INR values >2.5 (p < 0.001, p = 0.002 and p < 0.001, respectively), whereas CYP4F2 T carriers had a low risk of the same outcome (p = 0.009). In regards to combined genotypes, CYP4F2 had a significant effect on over-anticoagulation at the beginning of therapy except for the VKORC1 AA and CYP2C9*3 combination. CONCLUSION: In addition to VKORC1 and CYP2C9, CYP4F2 gene has a slight but significant role in reaching INR >2.5 during the first weeks of acenocoumarol therapy.
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Cerezo-Manchado et al. (2014) conducted a cohort in Patients starting acenocoumarol therapy (n=941). VKORC1, CYP2C9 and CYP4F2 genetic variants vs. Other genotypes was evaluated on Over-anticoagulation (INR >2.5) (p=<0.001). VKORC1 and CYP2C9 genotypes significantly increased the risk of over-anticoagulation (INR >2.5) (p<0.001 and p=0.002), while CYP4F2 T carriers had a lower risk (p=0.009).
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