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

Pharmacogenomics of Antithrombotic Drugs (PreMed PGx Study)

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.

Study Overview

• Status: Completed
• Conditions: Individuals With a Disease of Cardiovascular System
• Intervention / Treatment: Other: Non-interventional study

• Study Type: Observational
• Enrollment (Actual): 7005

Contacts and Locations

Study Locations

• Finland
  • Multiple Locations, Finland
    • To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: VTT Technical Research Centre of Finland
• Collaborators: Social Insurance Institution, Finland; Finnish Institute for Health and Welfare; Hospital District of Helsinki and Uusimaa; Hospital District of Southwestern Finland; Helsinki Biobank; THL Biobank; Auria Biobank
• Investigators: Study Director: Jari Ahola, VTT Technical Research Centre of Finland; Principal Investigator: Mark van Gils, PhD, VTT Technical Research Centre of Finland

Publications and helpful links

General Publications

• Vuorinen AL, Lehto M, Niemi M, Harno K, Pajula J, van Gils M, Lahteenmaki J. Pharmacogenetics of Anticoagulation and Clinical Events in Warfarin-Treated Patients: A Register-Based Cohort Study with Biobank Data and National Health Registries in Finland. Clin Epidemiol. 2021 Mar 8;13:183-195. doi: 10.2147/CLEP.S289031. eCollection 2021.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2019
• Primary Completion (Actual): April 28, 2020
• Study Completion (Actual): April 28, 2020

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: PreMed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No