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Randomized Controlled Trial
. 2015 Dec 28;10(12):e0145318.
doi: 10.1371/journal.pone.0145318. eCollection 2015.

A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation

Vittorio Pengo  1 , Carlo-Federico Zambon  2   3 , Paola Fogar  3 , Andrea Padoan  2   3 , Giovanni Nante  1 , Michela Pelloso  3 , Stefania Moz  2   3 , Anna Chiara Frigo  1 , Francesca Groppa  2 , Dania Bozzato  2   3 , Enrico Tiso  1 , Elisa Gnatta  3 , Gentian Denas  1 , Seena Padayattil Jose  1 , Roberto Padrini  2 , Daniela Basso  3 , Mario Plebani  2   3
Affiliations
Randomized Controlled Trial

A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation

Vittorio Pengo et al. PLoS One. .

Abstract

Genotype-guided warfarin dosing have been proposed to improve patient’s management. This study is aimed to determine whether a CYP2C9- VKORC1- CYP4F2-based pharmacogenetic algorithm is superior to a standard, clinically adopted, pharmacodynamic method. Two-hundred naïve patients with non-valvular atrial fibrillation were randomized to trial arms and 180 completed the study. No significant differences were found in the number of out-of-range INRs (INR<2.0 or >3.0) (p = 0.79) and in the mean percentage of time spent in the therapeutic range (TTR) after 19 days in the pharmacogenetic (51.9%) and in the control arm (53.2%, p = 0.71). The percentage of time spent at INR>4.0 was significantly lower in the pharmacogenetic (0.7%) than in the control arm (1.8%) (p = 0.02). Genotype-guided warfarin dosing is not superior in overall anticoagulation control when compared to accurate clinical standard of care.

Trial registration: ClinicalTrials.gov NCT01178034.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study Flow diagram.
–The diagram shows the progress through the phases of the randomized trial: enrolment, intervention allocation, follow-up, and data analysis.
Fig 2
Fig 2. Percentage of Time in the Therapeutic INR Range according to subgroup.
The percentage of time in the therapeutic INR range for pharmacogenetic arm (Genotype guided group) and control arm (Control group) are shown over the 19 day observational period.
Fig 3
Fig 3. Overall mean INR variations according to subgroup.
Comparison of finding in the pharmacogenetic arm (section A, Genotype guided group) and control arm (section B, Control group) during the 0–19 day time frame. The bars denote Standard Deviations, the dotted lines indicate the therapeutic margins. INR = International Normalized Ratio.
See this image and copyright information in PMC

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