Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Genetic Data Does Not Improve Anticoagulation Control with Warfarin

Published: Monday, December 09, 2013
Last Updated: Monday, December 09, 2013
Bookmark and Share
NIH-funded study shows genotyping adds no benefit when added to a clinically-guided dosing formula.

Combining genetic data with clinical information to determine the initial dosage of the blood thinner warfarin, used to prevent blood clots in the circulatory system, was no more effective in achieving stable anticoagulation than using only clinical information, according to a National Institutes of Health-funded clinical trial.

In addition, the study found that in African-Americans, anticoagulation control was lower in the genetics-based approach compared to the clinically-based method.

The results of the Clarification of Optimal Anticoagulation through Genetics (COAG) trial, supported by the NIH's National Heart, Lung, and Blood Institute, were presented at the American Heart Association (AHA) Scientific Sessions in Dallas. The study was published simultaneously in the New England Journal of Medicine.

"The use of genetic data holds great promise for predicting disease risk or determining optimal therapies, but it must be put to the test through clinical trials like this one to determine how to best use that information," said Gary H. Gibbons, M.D., director of the NHLBI. "This is especially true for complex drugs like warfarin whose action in our bodies is influenced by a variety of genetic, clinical and environmental factors."

Warfarin is the most commonly prescribed drug to prevent blood clots in conditions such as atrial fibrillation, deep vein thrombosis, or pulmonary embolism. Though warfarin is an effective therapy for many people with cardiovascular problems, the drug poses risks if improperly dosed. If dosed too high, warfarin can increase the risk of bleeding; if dosed too low, it can increase the risk of blood clots.

Proper dosing of warfarin is complicated because the drug interacts with many other common medications as well as some foods. When determining an initial dose, doctors often start with a standard dose and can take certain clinical indicators into account to alter that dose.

These clinical measures include age, body size, smoking status, and use of certain medications. During the initial weeks of therapy, the warfarin activity is monitored closely through blood tests, and adjustments are made as needed.

Recent research has suggested that variants of two genes, CYP2C9 and VKORC1, may be important in selecting the dose of warfarin needed for individual patients.

Based on these studies, dosing formulas have been developed that incorporate a person's genetic profile along with the patient's clinical characteristics to try and better predict the proper dose of warfarin - an approach known as pharmacogenetics.

However, the evidence supporting pharmacogenetics for warfarin has not been definitive; small clinical studies and some observational data have produced conflicting results. In addition, there have been differences noted in how accurate these dosing formulas are in different groups of patients. In particular, the formulas tend to be somewhat less accurate in African-Americans.

"Given the lack of definitive information on whether or not pharmacogenetics can improve the care of patients and the need to study a broad range of patients being treated with warfarin, we needed a large clinical trial like COAG to help resolve this important question," said Stephen Kimmel, M.D., of the Perelman School of Medicine at the University of Pennsylvania and principal investigator of the COAG trial.

COAG enrolled 1,015 patients beginning warfarin therapy and randomly assigned them to one of two dosing strategies. During the first five days of therapy, the participants would have their dosages determined and adjusted by a clinical formula or a pharmacogenetic formula. The participants were monitored for 23 additional days, and dosage changes were made using a standard approach. Participants and the treating physician were blinded to the strategy and the dose of warfarin.

Study investigators compared how much time the patients spent in their ideal therapeutic dosage range during the 28-day monitoring phase. Among all patients, the clinical and pharmacogenetic groups were virtually identical at 45.4 percent and 45.2 percent time in therapeutic range, respectively.

Among the 255 African-American participants, the pharmacogenetic formula provided only 35.2 percent time in therapeutic range compared to 43.5 percent for the clinical formula. African-Americans in the pharmacogenetic group generally took longer to reach an ideal dose compared to the clinical group (70 percent in the pharmacogenetic group reached their ideal range by day 14 compared to 87 percent in the clinical group). The African-Americans in the pharmacogenetic group did not experience any increased health issues like bleeding or clotting, however. There were also no differences in adverse events between the two dosing groups as a whole, and the total number of adverse events was low.

"These findings highlight the importance of developing and evaluating pharmacogenetic testing in patients from diverse racial and ethnic backgrounds," Gibbons said. "We are optimistic about the prospects of personalized, precision medicine, but we must make sure that we put these approaches through the same type of rigorous testing as any other prognostic test or clinical treatment strategy."

The COAG study was supported by NHLBI contract HHSN268200800003C and carried out at 18 hospitals and medical centers across the country. Yves Rosenberg, M.D., M.P.H., was the NHLBI project officer for COAG, and also served on the executive and steering committee.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
House Votes in Favor of Bill Boosting NIH Funding
The US House of Representatives today overwhelmingly voted in favor of a bill that would increase funding to the NIH by about $10 billion, help speed the development of new drugs, and advance precision medicine initiatives.
Monday, July 13, 2015
Linking Targeted Cancer Drugs to Gene Abnormalities
Investigators at the NIH have announced a series of clinical trials that will study drugs or drug combinations that target specific genetic mutations.
Wednesday, June 03, 2015
Genetic Link For Rare Intestinal Cancer
Researchers recommend screening for people with family history.
Thursday, April 16, 2015
Genetics Help Predict Heart Disease Risk, Statin Benefits
Researchers found that a set of genetic variants could identify people at risk for coronary heart disease and who would benefit most from statin therapy.
Tuesday, March 24, 2015
NIH Grants Aim To Decipher The Language Of Gene Regulation
The GGR program aims to develop new ways for understanding how the genes and switches in the genome fit together as networks.
Tuesday, January 06, 2015
Study Finds Genetic Clue To Menopause-Like Condition In Young Women
NIH-funded research may also contribute to understanding normal menopause.
Thursday, December 18, 2014
Researchers Conduct Comprehensive Genomic Study of Sub-Saharan Africans
New data resource will enhance disease research and genomic diversity studies.
Friday, December 05, 2014
Chromosome Region Linked to Gigantism
Duplication of gene on X chromosome appears to cause excessive growth.
Thursday, December 04, 2014
Comprehensive Genomic Study of Sub-Saharan Africans Conducted
New data resource will enhance disease research and genomic diversity studies.
Thursday, December 04, 2014
Scientists Looking Across Human, Fly and Worm Genomes Find Shared Biology
Studies reveal powerful commonalities in biological activity and regulation among species.
Thursday, August 28, 2014
Pinpointing Genes that Protect Against Frailty
Researchers at Albert Einstein College of Medicine of Yeshiva University have been awarded a $3.3M grant from the NIH to study the role of genetics in protecting against frailty.
Thursday, August 14, 2014
GTEx Project to Expand Functional Studies of Genomic Variation
Larger set of human tissues to be analyzed to contribute to a database and tissue bank that researchers can use to study how genomic variants influence gene activity.
Wednesday, August 06, 2014
NIH Funds $24M into Alzheimer’s Disease Genome Research
Scientists will analyze genome sequence data to identify gene risk, protective factors.
Tuesday, July 08, 2014
Underlying Genetics and Marker For Stroke Discovered
NIH-funded findings point to new potential strategies for disease prevention, treatment.
Friday, March 21, 2014
Scientific News
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
The Genetic Roots of Adolescent Scoliosis
Scientists at the RIKEN Center for Integrative Medical Sciences in collaboration with Keio University in Japan have discovered a gene that is linked to susceptibility of Scoliosis.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
How a Kernel Got Naked and Corn Became King
Ten thousand years ago, a golden grain got naked, brought people together and grew to become one of the top agricultural commodities on the planet.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Oxitec ‘Self-Limiting Gene’ Offers Hope for Controlling Invasive Moth
A new pesticide-free and environmentally-friendly way to control insect pests has moved ahead with the publication of results showing that Oxitec diamondback moths (DBM) with a ‘self-limiting gene’ can dramatically reduce populations of DBM.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!