Clarification of Optimal Anticoagulation Through Genetics (COAG) - Catalog

Name

Clarification of Optimal Anticoagulation Through Genetics (COAG)

Accession Number

HLB01331616a

Acronym

COAG

Related studies

BSI Study IDs

COAG

Is public use dataset

False

Keywords

Atrial Fibrillation

Thrombosis

Venous Thrombosis

Atrial Flutter

Arrhythmias, Cardiac

Heart Diseases

Cardiovascular Diseases

Pathologic Processes

Embolism and Thrombosis

Vascular Diseases

Warfarin

Anticoagulants

Has Study Datasets

True

Has Specimens

True

Specimen ID Type

Coded

Study Website

The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

False

Study type

Clinical Trial

Collection Type

Open BioLINCC Study

Cohort type

Adult

Interventions

Behavioral: Genotype-guided dosing algorithm for warfarin

Behavioral: Clinical-guided dosing algorithm for warfarin

Study Open Date (Data)

2016-03-08

Study Open Date (Specimens)

2022-07-11

Date materials available

2016-03-08

Last updated

None

Study period

September 2009 – November 2013

Study Contacts
NHLBI Division

DBDR

Classification

Blood Disease

HIV study classification

non-HIV

COVID study classification

non-COVID

Pre-Website # of Specimens Shipped

None

# of Returned Specimens

None

Conditions

Atrial Fibrillation
Atrial Flutter
Stroke
Venous Thrombosis

Objectives

The COAG trial tested whether genotype-guided dosing of warfarin improves anticoagulation control during the first 4 weeks of therapy when compared to clinical-guided dosing.

Background

Warfarin is highly efficacious at preventing thromboembolism, a condition associated with substantial morbidity and mortality. Individuals taking warfarin require dosage adjustments to maintain a therapeutic international normalized ratio (INR), particularly at the beginning of therapy. Out of range INR can increase risk of thromboembolism, bleeding, and early discontinuation of a highly useful therapy. Genotype-guided dosing of warfarin may be a more effective way of dosing warfarin when compared to only using clinical information. Observational studies have identified two genes, CYP2C9 and VKORC1, that are associated with variation in warfarin maintenance doses. Prior to the COAG trial, the effectiveness of genotype-guided dosing of warfarin had been limited to small clinical trials or observational studies, with equivocal results. Therefore comparison of the two strategies was needed to determine if use of genetic information is more effective in warfarin dosing than using clinical information.

Subjects

Participants were adults initiating warfarin therapy with a target international normalized ratio (INR) of 2 to 3 and an expected duration of therapy of at least 1 month. Exclusion criteria included current warfarin use, prior warfarin therapy with a known stable dose, and abnormal baseline INR (off warfarin). A total of 1015 subjects were enrolled in the study.

Design

The COAG study was a multicenter, double-blind, randomized trial that compared two approaches to guiding warfarin therapy initiation. Subjects were randomly assigned in a 1:1 ratio to a dosing strategy during the first 5 days of warfarin therapy. For each dosing strategy, a dose-initiation algorithm was used during the first 3 days of therapy, and a dose-revision algorithm was used on day 4, 5, or both. The algorithms for the genotype-guided dosing strategy included clinical variables and genotype data for CYP2C92, CYP2C93, and VKORC1. The algorithms for the clinically based dosing strategy included clinical variables only. If genotype information was not available for a patient in the genotype-guided dosing group before the administration of warfarin on any given day in the first 5 days, the clinical algorithm was used on that day.


During the first 4 weeks of therapy, patients and clinicians were unaware of the actual dose of warfarin that was administered. After the 5-day initiation period, dosage was adjusted during the first 4 weeks using standardized dose-adjustment techniques, starting with the doses predicted by the algorithms and making the same relative adjustments on the basis of the INR in the two study groups. Clinicians were informed of the relative dose change at each INR measurement but not the actual dose of warfarin. Subjects were to be followed for a total of 6 months.


The primary outcome was the percentage of time that the subject’s INR was in the therapeutic range (2 to 3) from the completion of the intervention period (day 4 or 5) through day 28 of therapy. Secondary outcomes included a composite outcome of any INR of 4 or more, major bleeding, or thromboembolism in the first 4 weeks.

Conclusions

Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy.


N Engl J Med. 2013 Dec 12; 369(24): 2283–2293.

Disease classification

Publications

Mat types

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    882 subjects (444 Genotype-Guided, 438 Clinically-Guided)


    Last Modified: July 22, 2022, 3:04 p.m.
  • Age
      Genotype-Guided Clinically-Guided All
    <30 35 26 61
    30-39 39 42 81
    40-49 54 80 134
    50-59 106 99 205
    60-69 100 90 190
    70-79 71 67 138
    80+ 39 34 73
     

    Last Modified: July 22, 2022, 3:04 p.m.
  • Sex
      Genotype-Guided Clinically-Guided All
    Male 235 216 451
    Female 209 222 431
     

    Last Modified: July 22, 2022, 3:04 p.m.
  • Race
      Genotype-Guided Clinically-Guided All
    AA only 114 115 229
    White only 313 297 610
    Asian only 6 10 16
    Other 11 16 27
     

    Last Modified: July 22, 2022, 3:04 p.m.

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

  • Material Types

    DNA


    Last Modified: July 22, 2022, 3:04 p.m.
  • General Freeze/Thaw Status

    All samples have 0 thaws


    Last Modified: July 22, 2022, 3:04 p.m.
  • Visits (Vials)
      DNA
    Baseline 2455
     

    Last Modified: July 22, 2022, 3:04 p.m.
  • Visits (Subjects)
      DNA
    Total number of subjects Average vials per subject
    Baseline 828 2.96
     

    Last Modified: July 22, 2022, 3:04 p.m.