A multiplex assay to detect variations in the CYP2C9, VKORC1, CYP4F2 and APOE genes involved in acenocoumarol metabolism

López-Parra, Ana Marı́a; Borobia, Alberto M.; Baeza, Carlos M.; Arroyo-Pardo, Eduardo; Carcas, Antonio J.

doi:10.1016/j.clinbiochem.2012.08.005

Cited by 6 publications

(2 citation statements)

References 9 publications

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“…In the recruitment visit, two 3 ml tubes of blood will be collected from all participants for genotyping of CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), VKORC1 ( − 1639 G → A = rs9923231), CYP4F2 (rs2108622), and APOE (8016 C → T = rs7412), using a previously developed multiplex technique [28]. Measurements will be performed in a centralized manner at the Laboratory of Population Genetics of the Department of Forensics at the Universidad Complutense de Madrid.…”

Section: Methodsmentioning

confidence: 99%

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

Carcas

Borobia

Velasco

et al. 2012

Trials

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BackgroundHemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE).Methods and designThis is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment.DiscussionTo date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety.Trial registrationEudra CT. Identifier: 2009-016643-18.

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Section: Methodsmentioning

confidence: 99%

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

Carcas

Borobia

Velasco

et al. 2012

Trials

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“…Genotyping was performed by the Laboratory of Population and Forensic Genetics of the Department of Legal Medicine, Psychiatry and Pathology of the Faculty of Medicine at the Complutense University of Madrid, according to a previously described multiplex technique [34]. Genotyping included CYP2C9*2…”

Section: Genotypingmentioning

confidence: 99%

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial

Tong¹,

Borobia

Quintana-Díaz

et al. 2021

JCM

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Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

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Pharmacogenetics of Oral Anticoagulants

Jiménez-Varo

Cañadas-Garre

Aguilera

et al. 2013

Omics for Personalized Medicine

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A multiplex assay to detect variations in the CYP2C9, VKORC1, CYP4F2 and APOE genes involved in acenocoumarol metabolism

Cited by 6 publications

References 9 publications

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial

Pharmacogenetics of Oral Anticoagulants

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