Background:
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-guided and clinically guided dosing of
warfarin in
atrial fibrillation (AF), deep-vein thrombosis (DVT), and pulmonary embolism (PE) within the first 5 days after the introduction of therapy.
Methods:
In this single-center, single-blinded, randomized, controlled trial including patients of both sexes, ≥18 years of age, and diagnosed with AF, DVT, or PE, a total of 205 consecutive patients were allocated into the group where
warfarin therapy was genotype-guided pharmacogenetics guided (PHG), and where it was adjusted according to the clinical parameters non pharmacogenetics guided (NPHG). Genotyping of
CYP2C9*2, *3, and
VKORC1 was performed using the real-time polymerase chain reaction 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 2 consecutive measurements.
Results:
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, 0–23;
P = 0.040]. There was no significant difference in other 2 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%) (odds ratio = 3.13, 95% confidence interval, 0.92–10.98;
P = 0.039).
Conclusions:
CYP2C9 and
VKORC1 genotype-guided dosing of
warfarin may be beneficial in patients diagnosed with AF. There is no evidence for such conclusion in patients with DVT and PE.
