Genetic screening unnecessary in elderly warfarin patients
MedWire News: Genetic testing does not improve the accuracy of dosing algorithms among elderly inpatients starting warfarin therapy, according to research published in the Journal of Thrombosis and Haemostasis.
French researchers investigated whether incorporating vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotype information into different models based on clinical data and international normalized ratios (INRs) helped predict the warfarin maintenance dose.
However, "once treatment is started using induction doses tailored for elderly patients, the contribution of VKORC1 and CYP2C9 genotypes in dose refinement is negligible compared to two INR values measured during the first week of treatment," report Virginie Siguret (INSERM U765, Paris, France) and colleagues.
They prospectively enrolled 187 elderly inpatients (mean age=85.6 years) who all started on warfarin using the same "geriatric dosing algorithm" in which each patient received a 4 mg induction dose of warfarin on days 0-2, followed by a maintenance dose that was adjusted according to the INR on days 3 and 6.
The researchers found that at baseline (day 0) the clinical model - based on age, indication for warfarin, and INR - did not accurately predict the maintenance dose (R2=0.10, meaning that the clinical model predicted less than 10% of the variability in the maintenance dose).
Adding the VKORC1 and CYP2C9 genotypes to the model increased the accuracy to 31%, indicating that genetic factors were the main determinants of the maintenance dose at this stage, they say.
However, assessment on day 3 showed that the INR on that day was the strongest predictor of the maintenance dose, at 51%. Furthermore, VKORC1 genotype provided no further information, while CYP2C9 genotype added only 3% to the accuracy of the model.
At day 6, neither genotype helped to predict the maintenance dose, which was predicted by the clinical model with an accuracy of 80%.
When the researchers evaluated the effectiveness of the geriatric dosing algorithm in predicting the daily warfarin maintenance, they found that the predicted dose correlated closely with the observed maintenance dose based on the INR on days 3 (R2=0.77) and 6 (R2=0.81) The algorithm underestimated (>1 mg) and overestimated the dose (>1 mg) in fewer than 10% and 2% of patients, respectively.
This simple algorithm, which is inexpensive and widely applicable, "safely and accurately predicts the warfarin maintenance dose in elderly inpatients at treatment initiation without requiring genetic information," Siguret and co-authors conclude.
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By Laura Dean