Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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 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

Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Researchers Identify Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Saturday, October 31, 2015
Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Friday, October 23, 2015
Charting Genetic Variation Across the Globe
An international team of scientists has created the world’s largest catalog of human genetic differences in populations around the globe.
Tuesday, October 20, 2015
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Tuesday, October 20, 2015
Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Dormant Viral Genes May Awaken to Cause ALS
NIH human and mouse study may open an unexplored path for finding treatments.
Thursday, October 01, 2015
Scientists Create World’s Largest Catalog of Human Genomic Variation
An international team of scientists from the 1000 Genomes Project Consortium has created the world’s largest catalog of genomic differences among humans, providing researchers with powerful clues to help them establish why some people are susceptible to various diseases.
Thursday, October 01, 2015
Genetic Adaptations to Diet and Climate
Researchers found genetic variations in the Inuit of Greenland that reflect adaptations to their specific diet and climate.
Tuesday, September 29, 2015
Scientific News
Tardigrade's Are DNA Master Thieves
Tardigrades, nearly microscopic animals that can survive the harshest of environments, including outer space, hold the record for the animal that has the most foreign DNA.
The Secret Behind the Power of Bacterial Sex
Migration between different communities of bacteria is the key to the type of gene transfer that can lead to the spread of traits such as antibiotic resistance, according to researchers at Oxford University.
Farming’s in Their DNA
Ancient genomes reveal natural selection in action.
GMO Food Animals Should be Judged by Product, Not Process
In a world with a burgeoning demand for meat, milk and eggs, regulatory policies around the use of biotechnologies in agriculture need to be based on the safety and attributes of those foods rather than on the methods used to produce them, says a UC Davis animal scientist.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
Gene Drive Reversibility Introduces New Layer of Biosafety
Ability to introduce or reverse the spread of genetic traits through populations could one day improve pest management and disease control.
RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
University of Glasgow Researchers Make An Impact in 60 Seconds
Early-career researchers were invited to submit an engaging, dynamic and compelling 60 second video illuminating an aspect of their research.
Metabolic Profiles Distinguish Early Stage Ovarian Cancer with Unprecedented Accuracy
Studying blood serum compounds of different molecular weights has led scientists to a set of biomarkers that may enable development of a highly accurate screening test for early-stage ovarian cancer.
Dead Bacteria to Kill Colorectal Cancer
Scientists from Nanyang Technological University (NTU Singapore) have successfully used dead bacteria to kill colorectal cancer cells.
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos