Pharmacogenomics of Antithrombotic Drugs -a Register Linkage Study With National Registries and Biobanks in Finland

Study Overview
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Brief Summary
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This is a retrospective cohort study linking data from Finnish Biobanks (Helsinki Biobank, Auria Biobank and THL Biobank), laboratory databases, and national registries of Social Insurance Institution of Finland (Kela) and the National Institute of Health and Welfare (THL) to investigate pharmacogenomics of antithrombotic drugs in the Finnish population. The purpose of the study is to assess clinical and economic aspects of using genomic data in the context of antithrombotic drug therapy. Based on earlier research, data regarding variant alleles in CYP2C9 and VKORC1 will be used in the primary analyses. Individuals with and without specific variant alleles are compared in respect to their clinical response to warfarin therapy. Warfarin-treated individuals are also analysed in relation to other clinical outcomes and a wide range of healthcare encounters. The explorative part of the study will employ data-driven classification methods to explore genotype-phenotype associations for a larger group of antithrombotic drugs including direct oral anticoagulants, clopidogrel and heparins and possible interactions with other drugs. In this part, 26 gene variants identified in literature will be used. The retrospective follow-up time for the study participants is from January 2007 to December 2018, or 2 years prior the first anticoagulant drug is purchased until 6 months after the last purchase.

Official Title
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Pharmacogenomics of Antithrombotic Drugs (PreMed PGx Study)

Conditions
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Individuals With a Disease of Cardiovascular System

Intervention / Treatment
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* Other: Non-interventional study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genotyped for CYP2C9/rs1799853, CYP2C9/rs1057910 and VKORC1/rs9923231 Diagnosed with at least one of the following: Atrial Fibrillation and Flutter (I48) Ischemic Heart Disease (I20-I25) Cerebrovascular disease (I63,I65,I66, 167.2, I69.3-I69.8) Atherosclerosis (I70) Pulmonary embolism (I26) Phlebitis and thrombophlebitis (I80) Portal vein thrombosis (I81) Other venous embolism and thrombosis (I82) Purchased at least one of the following drugs between January 1st 2007 - December 31st 2018: Anticoagulants: Warfarin, Dabigatran, Apixaban, Rivaroxaban, Edoxaban, Heparin, Enoxaparin, Dalteparin Antiplatelets: Clopidogrel, Ticagrelor, Acetylsalicylic acid Exclusion Criteria: Permanent residence in Finland less than 12 months during the follow-up period Purchase of any of the antithrombotic drugs listed above between January 1st 2005 - December 31st 2006

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Non-interventional study|This is a non-interventional study. Patients will be treated with any treatment deemed appropriate by the patient's physician.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bleeding complications | Incidence of bleeding complications in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Therapeutic Range (TTR) | TTR during first three months in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Time to reach therapeutic range | Time to reach therapeutic range in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Time-weighted mean INR | INR (time-weighed mean) during the first month in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Incidence of outpatients visits | Incidence of outpatient visits caused by bleeding in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Incidence of laboratory visits | Incidence of laboratory visits related to warfarin treatment in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| The number of laboratory tests | The number of performed laboratory tests laboratory tests related to warfarin treatment in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Incidence of emergency room (ER) visits | Incidence of ER visits caused by bleeding, myocardial infarction or cerebral infarction in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Indicidence of hospital admissions | Hospitalizations caused by bleeding, myocardial infarction or cerebral infarction in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| The number of hospital inpatient days | The number of inpatient days caused by bleeding, myocardial infarction or cerebral infarction in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment | 
| Incidence of medical procedures | Incidence of medical procedures caused by bleeding, myocardial infarction or cerebral infarction in warfarin-treated individuals | During warfarin treatment and beyond 6 months after the treatment |