engleski

Warfarin dosing according to the genotype- guided algorithm is most beneficial in patients with atrial fibrillation

Observational studies have indicated potential benefits of CYP2C9 and VKORC1 guided dosing of warfarin but randomized clinical trials have resulted in contradictory findings. One of the reasons for contradiction may be the negligence of possible differences between warfarin indications. This study aims to determine efficacy and safety of genotype- and clinically guided dosing of warfarin in atrial fibrillation (AF), deep-vein thrombosis (DVT), and pulmonary embolism (PE) within the first five days after the introduction of therapy.In this single-center, single-blinded, randomized, controlled trial including patients of both sexes, ≥18 years of age, diagnosed with AF, DVT, or PE, a total of 205 consecutive patients were allocated into the group where warfarin therapy was genotype-guided (PHG), and where it was adjusted according to the clinical parameters (NPHG). Genotyping of CYP2C9*2, *3 and VKORC1 was performed using the Real-Time PCR method. The primary outcomes were the percentage of time in the therapeutic international normalized ratio (INR) (2.0-3.0) range and the percentage of patients who achieved a stable anticoagulation defined as the INR (2.0-3.0) range in at least two consecutive measurements.In patients with AF, the percentage of time spent in the therapeutic range of INR was higher in the PHG group (mean=26% (SD 25.0)), than in the NPHG group (mean=14% (SD 18.6)), (Δ=12 ; 95% confidence interval (CI) 0-23 ; p=0.040). There was no significant difference in other two indications for warfarin treatment. A stable dose of warfarin was achieved in a statistically higher number of patients in the PHG group 14/30 (47%), than in the NPHG group 7/32 (22%) (OR=3.13, 95% CI 0.92-10.98 ; p=0.039).CYP2C9 and VKORC1 genotype-guided dosing of warfarin may be beneficial in patients diagnosed with atrial fibrillation. There is no evidence for such conclusion in patients with DVT and PE.

warfarin ; atrial fibrillation ; CYP2C9 ; VKORC1 ; international normalized ratio (INR)

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