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.

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

The study population consists of adults diagnosed with a disease of cardiovascular system and genotyped for variants in CYP2C9 and VKORC1, and who have used antithrombotic drugs between January 1st 2007 - December 31st 2018.