Harno, Kari

Lehto, Mika

Lähteenmäki, Jaakko

Niemi, Mikko

Vuorinen, Anna-Leena

Wolf, Maija

English

Aim: With aging population, the need for individualised antithrombotic treatments will expand. Pharmacogenetic studies have established associations between a number of genetic variants and adverse drug responses with antithrombotic drugs. This abstract presents the design of a register linkage study, which aims to investigate the clinical and economic feasibility of using genomic data in the context of antithrombotic drug therapy.Methods: This is a retrospective cohort study linking data from three Finnish biobanks (Helsinki Biobank, Auria Biobank and THL Biobank), national registries of National Institute of Health and Welfare (THL) and the Social Insurance Institution (Kela) and laboratory databases to investigate the feasibility of using genotype data in antithrombotic therapy. Based on earlier research, data regarding 23 genetic variants will be used for the analyses. Genotype data generated within the FinnGen project and scheduled to be available for biobank research during 2019 will be used. Individuals with and without specific variant alleles are compared in respect to their response to warfarin therapy measured by the incidence of bleeding complications and the time in therapeutic range (TTR) parameter. Individuals are also analysed in relation to other clinical outcomes and healthcare encounters, and possible interactions with other drugs. Furthermore, the explorative part of the study will employ data-driven classification methods to investigate genotype-phenotype associations for a larger group of antithrombotic drugs, including direct oral anticoagulants, clopidogrel and heparins.Results: Data permit applications to the registry holders have been submitted during the first quarter of 2019. The first results are expected to be available during 2019. The early estimate on sample size indicates that by combining data from three biobanks approximately 2600 adults with genotype data will be available which suffices the predefined power for the study. Beyond the clinical results, the study sheds light on the process of combining data from several biobanks. Such information is expected to be valuable for the on-going development of centralized register data and biobank services in Finland. Conclusions: The study increases the understanding of pharmacogenomics of antithrombotic drugs in the Finnish population and assesses the need for genotype-guided therapy to improve the outcomes of antithrombotic therapies.<br/

VTT Research System

ObjectivesTo investigate clinical and economic feasibility of usinggenomic data in the context of antithrombotic drug therapy bylinking data from Finnish biobanks and national registries.The specific objectives are:1. To investigate clinical response to warfarin therapy inindividuals with and without specific genetic variants2. To assess the clinical and economic impact of usinggenotype data in guiding warfaring therapy3. To employ data-driven classification methods to exploregenotype-phenotype associations for antithromboticdrugs, including direct oral anticoagulants, clopidogreland heparinsData sourcesThe following data and data sources are intended to be used: • Genotype data (Helsinki Biobank, THL Biobank, Auria Biobank)• Laboratory data (laboratory registers)• Healthcare encounters (National Institute for Health and Welfare)• Drug purchases (Social Insurance Institution)• Electronic health recordsParticipantsInclusion criteria:• ≥ 18 years of age• Genotyped for variants in CYP2C9 and VKORC1• Diagnosed with a disease of cardiovascular system.• Purchased at least one of the following antithrombotic drugsbetween 1.1.2007 - 31.12.2018:• Warfarin, Dabigatran, Rivaroxaban, Apixaban, Edoxaban, Heparin, Enoxaparin, Dalteparin, Clopidogrel, Ticagrelor, Acetylsalicylic acidSample size: 2678 patients are required to detect a risk ratio(RR) of 1.8 for bleeding complications in carriers of variantalleles CYP2C9*2 and CYP2C9*3 (α=0.05, power=0.9).Outcomes measures• Bleeding complications in warfarin users• Time in Therapeutic Range (TTR) in warfarin users• Drug dosage in warfarin users• Healthcare encounters in warfarin users• Clinical response to other antithrombotic drugs• Interactions with other drugsContactAnna-Leena VuorinenTel. +358408485966 anna-leena.vuorinen@vtt.fiVTT – beyond the obviouswww.vttresearch.comPharmacogenomics of antithrombotic drugs – a novel study design and data collection approach using Finnish biobanks and national registriesAnna-Leena Vuorinen1, Jaakko Lähteenmäki1, Mika Lehto2, Kari Harno3, Maija Wolf4, Mikko Niemi51 VTT Technical Research Centre of Finland Ltd, 2 Hospital District of Helsinki and Uusimaa, 3 University of Eastern Finland, 4 Medaffcon Oy, 5 University of HelsinkiBackgroundAdverse drug reactions cause hospitalizations and evenpremature deaths. Pharmacogenetic studies have identified anumber of gene variants that cause adverse drug responsesin individuals using antithrombotic drugs. Certain genevariants affect drug metabolism increasing the risk forbleeding.Figure 1. Prevalence of CYP2C9 variant alleles and theirassociation with warfarin therapy.Figure 2. Data sources.Status and next steps• Preparatory phase on-going (data permit applications and contracts)• Data analysis planned to begin in September 2019 (FinnGen genome data to be released for biobank studies)• The study is carried out in the framework of the PreMed projectPreMed projectwww.vtt.fi/premed

Pharmacogenomics of antithrombotic drugs –a novel study design and data collection approach using Finnish biobanks and national registries

https://cris.vtt.fi/files/26783110/NBCC2019_Vuorinen.pdf

Pharmacogenomics of antithrombotic drugs –a novel study design and data collection approach using Finnish biobanks and national registries

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