Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients

Bazan, Naglaa Samir; Sabry, Nirmeen A.; Rizk, Amal; Mokhtar, S; Badary, Osama A.

doi:10.1007/s11096-012-9678-3

Cited by 18 publications

(23 citation statements)

References 30 publications

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“…We demonstrated that the Gage genetic algorithm predicted the largest proportion of patients within ideal dose (65%) followed by IWPC algorithm (58%), warfarin label (37%), Gage clinical algorithm (37%), and IWPC clinical algorithm (36%). This is in agreement with those reported by Finkelman et al [25] and in discordance with Bazan et al [13] in which the warfarin dosing table predicted the largest proportion of patients within ideal dose (28.6), followed by the Gage genetic algorithm (27%), the IWPC genetic algorithm (25.4%), the Gage clinical algorithm (23.8), and the IWPC clinical algorithm (22.4%). In this study, the genetic algorithms predicted warfarin dose in only 25% of patients for the Gage genetic algorithm and 32% for the IWPC genetic algorithm.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, the genetic algorithms predicted warfarin dose in only 25% of patients for the Gage genetic algorithm and 32% for the IWPC genetic algorithm. These results are in agreement with Roper et al [26] and in discordance with Bazan et al [13] in which the Gage and IWPC genetic algorithms predicted a warfarin dose in 57.1% of their cohort of Egyptian patients. The discordance of our data from that reported by Bazan et al [13] could be attributed to the larger sample size and strict exclusion criteria in our study and more percentage of patients in their study taking warfarin ≥7 mg/day (44.4 vs. 30% in the current study).…”

Section: Discussionsupporting

confidence: 89%

“…Furthermore, data from previous reports addressing the value of pharmacogenetic testing in warfarin management in Egyptian patients were infrequent, controversial, and included different polymorphisms [13,14]. The aim of this study was to demonstrate the validity of pharmacogenetic dosing algorithms in Egyptian patients on warfarin therapy.…”

Section: Introductionmentioning

confidence: 97%

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Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

et al. 2018

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Background/Aims: Data from previous reports, addressing the significance of genotype-guided dosing of warfarin in Egyptian patients, are infrequent and controversial. This study is aimed at demonstrating the validity of genetic dosing algorithms in Egyptian patients on warfarin therapy. Methods: A total of 100 Egyptian patients on a stable maintenance daily dose of warfarin were enrolled. The predicted warfarin dose for each patient was calculated using the warfarin dosing table, the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) clinical algorithms and the Gage and the IWPC genetic algorithms and compared to the actual dose. The accuracy of warfarin dosing algorithms was assessed by using the linear regression analysis. Results: The most accurate model in predicting the ideal dose was the Gage genetic algorithm by R² of 50.4% and the IWPC genetic algorithm by R² of 42.3%, followed by the warfarin dosing table by R² of 19.1%, and the Gage clinical algorithm by R² of 18.9% and the least accurate was the IWPC clinical algorithm by R² of 9.4%. Conclusions: The Gage genetic warfarin dosing algorithm is the best model that could be implemented in Egyptian patients starting warfarin therapy.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 97%

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Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

et al. 2018

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“…To our knowledge, there were no warfarin pharmacogenomic studies carried in Egypt, with the exception of only three studies [26,27,30] in the preceding 2 years. The novel attribute of our study was the development of a warfarin dosing algorithm based on the genetic and nongenetic factors of the study cohort, and the validation of the calculated warfarin dosing algorithm in a different cohort with a significant positive correlation observed between the predicted warfarin dose and the actual prescribed dose.…”

Section: Discussionmentioning

confidence: 99%

Validation of a Proposed Warfarin Dosing Algorithm Based on the Genetic Make-Up of Egyptian Patients

et al. 2013

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VKORC1 (1173C>T) contributes to the warfarin dose variability. Patients' age and genetic variants of VKORC1 account for nearly 20.5% of the variability in warfarin dose required to achieve an INR of 2-3. The success of a prediction equation based on these variables was proved in a different cohort: the predicted dose correlated significantly with the maintenance dose and the equation was more successful among patients with a dose≥35 mg/week. The results of the warfarin algorithm we developed were comparable with those of the IWPC and Gage algorithms with the advantage of using one SNP (VKORC1 1173C>T) only. This represents an economic advantage in our community. Replication of this study in a larger cohort of patients is necessary before translation of this knowledge into clinical guidelines for warfarin prescription.

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“…Un ejemplo de ello fue la menor exactitud de predicción del algoritmo del IWPC en una muestra de pacientes egipcios (16). Incluso en grupos étnicos como los han de China, ha sido necesario incluir otras variables predictoras como el gen CYP4F2 (17).…”

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Predicción de sensibilidad a la warfarina basada en VKORC1 y CYP2C9 en pacientes de diferentes lugares de Colombia

2015

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Contribución de los autores:Ricardo A. Cifuentes: concepción del proyecto, genotipificación y análisis de datos Todos los autores participaron en la captación de los pacientes, la recolección de datos, la interpretación de los resultados y la escritura del manuscrito.Predicción de la sensibilidad a la warfarina con base en polimorfismos de los genes VKORC1 y CYP2C9 en pacientes colombianos Introducción. La validación de los factores predictores de la sensibilidad a la warfarina es importante para evitar las hemorragias asociadas con la terapia anticoagulante. En los estudios previos hechos en Colombia con polimorfismos de los genes VKORC1 y CYP2C9, se reportaban algoritmos con rendimientos diferentes para explicar la variación de las dosis, pero no se evaluaba la predicción de la sensibilidad a la warfarina. Objetivo. Determinar la exactitud del análisis farmacogenético de los polimorfismos *2 y *3 en el gen CYP2C9 y 1639G>A en el gen VKORC1 para predecir la sensibilidad a la warfarina en pacientes del Hospital Militar Central, un centro de referencia que atiende pacientes de diferentes lugares de Colombia. Materiales y métodos. Se recopilaron los datos demográficos y clínicos de 130 pacientes que habían recibido una dosis estable de warfarina durante más de dos meses. Se obtuvieron sus genotipos mediante un análisis de curvas de fusión, y, después de verificar el equilibrio de Hardy-Weinberg de los polimorfismos, se hizo un análisis estadístico con enfoque multivariado y predictivo.Resultados. Se construyó un modelo farmacogenético que explicó el 52,8 % de la variación de la dosis (p<0,001), solo 4 % por encima del rendimiento obtenido con los mismos datos usando el algoritmo del International Warfarin Pharmacogenetics Consortium. El modelo predictivo de sensibilidad logró 77,8 % de exactitud e incluyó como factores la edad (p=0,003), los polimorfismos *2 y *3 (p=0,002) y el polimorfismo 1639G>A (p<0,001). Conclusiones. Estos resultados en una población mestiza colombiana respaldan la validez de la predicción de la sensibilidad a la warfarina basada en los polimorfismos de los genes VKORC1 y CYP2C9. Prediction of sensitivity to warfarin based on VKORC1 and CYP2C9 polymorphisms in patients from different places in Colombia Introduction: In the search to prevent hemorrhages associated with anticoagulant therapy, a major goal is to validate predictors of sensitivity to warfarin. However, previous studies in Colombia that included polymorphisms in the VKORC1 and CYP2C9 genes as predictors reported different algorithm performances to explain dose variations, and did not evaluate the prediction of sensitivity to warfarin. Objective: To determine the accuracy of the pharmacogenetic analysis, which includes the CYP2C9 *2 and *3 and VKORC1 1639G>A polymorphisms in predicting patients' sensitivity to warfarin at the Hospital Militar Central, a reference center for patients born in different parts of Colombia. Materials and methods: Demographic and clinical data were obtained from 130 patients with stable doses of warfari...

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Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients

Abstract: Our study showed that genotype-based dosing improved prediction of warfarin therapeutic dose beyond that available with the fixed-dose approach or the clinical algorithms, especially in the low-dose group. However, the two pharmacogenetic algorithms were the most accurate.

Cited by 18 publications

References 30 publications

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Validation of a Proposed Warfarin Dosing Algorithm Based on the Genetic Make-Up of Egyptian Patients

Predicción de sensibilidad a la warfarina basada en VKORC1 y CYP2C9 en pacientes de diferentes lugares de Colombia

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