Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands

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From: Pharmacogenomics(Vol. 16, Issue 2)
Publisher: Future Medicine Ltd.
Document Type: Article
Length: 6,628 words
Lexile Measure: 1550L

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Author(s): Talitha I Verhoef aff1 aff2 , William K Redekop aff3 , Anthonius de Boer aff1 , Anke Hilse Maitland-van der Zee [*] aff1


acenocoumarol; atrial fibrillation; health economics; pharmacogenetics; phenprocoumon


Many observational studies have investigated the pharmacogenetics of coumarin anticoagulants such as warfarin, acenocoumarol and phenprocoumon [ 1-4 ]. These drugs are frequently prescribed for patients with atrial fibrillation to decrease the risk of stroke, but also for the treatment and prevention of venous thromboembolism [5 ]. Some genetic polymorphisms have been shown to be associated with the required dose and thereby also with the risk of adverse treatment outcomes, such as bleeding or thromboembolism [2 ]. Polymorphisms in the VKORC1 gene, coding for the main target enzyme of the drugs, and the CYP2C9 gene, coding for the main metabolizing enzyme, together account for approximately one third of the variability in dose requirements among different patients [3,6 ]. Several dosing algorithms have therefore been developed including genetic information, next to patient characteristics such as age, gender, height and weight [7 ].

Until recently, the clinical effectiveness of these algorithms had not been tested in acenocoumarol or phenprocoumon users. For warfarin users, some trials have been published, but these were not able to provide convincing evidence [7 ]. By the end of 2013, three large randomized controlled trials on pharmacogenetic-guided dosing of coumarin anticoagulants had been published [ 8-10 ]. One of these trials included acenocoumarol users from The Netherlands and Greece and phenprocoumon users from The Netherlands [8 ]. In this trial (the acenocoumarol and phenprocoumon arms of the European Pharmacogenetics of Anticoagulant Therapy [EU-PACT] trial - NCT01119261 and NCT01119274), a pharmacogenetic-guided algorithm based on age, gender, height, weight, amiodarone use and VKORC1 and CYP2C9 genotype was compared with an algorithm with the same patient characteristics, except the genotype information. This was done because it was expected that an algorithm based on patient characteristics only would perform better than the current standard care (all patients receive the same dose during the first days of therapy and this dose is adjusted after measuring the anticoagulant effect using an international normalized ratio [INR] test).

The pharmacogenetic algorithm did not significantly improve the primary outcome of time in therapeutic INR range in the first 12 weeks of therapy. However, it did improve the time in therapeutic INR range in the first 4 weeks (52.8 vs 47.5%; p = 0.02) [8 ]. Because performing a genetic test to assess the patients' genotype will require extra costs, it is important to investigate the cost-effectiveness of this test. The aim of this study is therefore to investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands. In The Netherlands, only phenprocoumon and acenocoumarol are prescribed (not warfarin). This study will therefore focus on phenprocoumon as well as acenocoumarol.

Materials & methods

Model structure

A decision-analytic Markov model was used to analyze the cost-effectiveness of a pharmacogenetic algorithm compared with a clinical algorithm for phenprocoumon and acenocoumarol. The model was...

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Gale Document Number: GALE|A413526797