Featured Research

from universities, journals, and other organizations

No benefit found to selecting dose of blood thinner based on patients' genetic makeup

Date:
November 19, 2013
Source:
University of Pennsylvania School of Medicine
Summary:
A new study led by researchers has determined that a gene-based method for selecting patients' doses of the popular heart medication warfarin is no better than standardized dosing methods.

A new study led by researchers at the Perelman School of Medicine at the University of Pennsylvania has determined that a gene-based method for selecting patients' doses of the popular heart medication warfarin is no better than standardized dosing methods. The study was presented today at the 2013 Scientific Sessions of the American Heart Association and published simultaneously in the New England Journal of Medicine.

"There has been much interest in the medical community about the utility of pharmacogenetics -- using information about a person's genetic makeup to choose the drugs and drug doses that are most likely to work well for that particular person -- to help better personalize treatments for patients and improve drug safety and efficacy," said lead study author Stephen Kimmel, MD, MSCE, professor of Medicine and Epidemiology at Penn Medicine. "Warfarin therapy has served as a model for the promise of a gene-based approach to patient care, but we needed a large, prospective clinical trial to determine if a patient's genetic information provides the added benefit above and beyond what can be obtained simply with clinical information."

Warfarin is a blood thinner used to prevent clots and is generally considered to be a very effective medication, but dosing must be properly adjusted for each patient, who are closely monitored for complications. Approximately 2 million Americans, primarily older patients, take warfarin to keep blood from excessive clotting, or coagulation. Currently, doctors face major challenges in determining the right dose of warfarin for each patient because individuals vary widely in how quickly their bodies' break down and respond to the drug. Taking too much warfarin could result in bleeding problems and taking too little warfarin will not stop clots from forming.

Previous research has shown that two genes, CYP2C9 and VKORC1, which vary among different individuals, can influence warfarin's effectiveness. In 2007 and 2010, the FDA worked with the makers of warfarin drug products to modify the product label to indicate that a patient's genetic makeup may affect how he or she responds to the drug and that genetic information might be useful in determining the optimal starting dose.

To find out whether these genes could help clinicians prescribe an optimal dose, the Clarification of Optimal Anticoagulation through Genetics (COAG) trial -- consisting of 18 clinical sites across the country and funded by the National Heart, Lung and Blood Institute (NHLBI) -- tested two approaches for determining the best initial dose of warfarin in patients who were expected to need therapy for at least one month or longer -- by clinical information alone or by clinical information plus specific genetic information. The four-year study included 1,015 patients randomly assigned to one of two groups during the first five days of initiating warfarin therapy.

For the patients in the clinical-based dosing group, the initial warfarin dose was determined using step-by-step procedures based only on information about clinical factors, such as age, sex, weight, ethnicity, and the use of other medications. In the gene-based dosing group, the initial dose was determined using this same clinical information as well as information about the patient's genetic makeup, including analyzing the participants' DNA for the CYP2C9 and VKORC1 genes. Patients and their providers were blinded to the dose of warfarin for the first month of therapy.

The researchers found that there was no difference among the two groups in mean percentage of time in therapeutic range (PTTR) for the medication (45.2 percent in the pharmacogenetic-dosing group versus 45.4 percent in the clinical-guided dosing group) at four-weeks. There was, however, a statistically significant difference by race. Among African Americans, the mean PTTR for the pharmacogenetic-guided dosing group was less than that for the clinical-guided dosing group -- 35.2 percent versus 43.5 percent, respectively. Pharmacogenetic-based dosing also led to more over-anticoagulation and a longer time to first therapeutic levels of the warfarin among African Americans.

The authors note that despite the positive results from other smaller studies analyzing the benefits of gene-based prescribing therapy, the results of this trial do not support the hypothesis that initiating warfarin therapy at a pharmacogenetic-predicted maintenance dose improves anticoagulation control over clinical methods. They point out that previous studies were primarily conducted at single clinical sites, were not blinded, and involved a limited number participants. They conclude that the COAG trial emphasizes the importance of performing large randomized trials for additional pharmacogenetics approaches, particularly for complex medicine regimens such as warfarin.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Stephen E. Kimmel, Benjamin French, Scott E. Kasner, Julie A. Johnson, Jeffrey L. Anderson, Brian F. Gage, Yves D. Rosenberg, Charles S. Eby, Rosemary A. Madigan, Robert B. McBane, Sherif Z. Abdel-Rahman, Scott M. Stevens, Steven Yale, Emile R. Mohler, Margaret C. Fang, Vinay Shah, Richard B. Horenstein, Nita A. Limdi, James A.S. Muldowney, Jaspal Gujral, Patrice Delafontaine, Robert J. Desnick, Thomas L. Ortel, Henny H. Billett, Robert C. Pendleton, Nancy L. Geller, Jonathan L. Halperin, Samuel Z. Goldhaber, Michael D. Caldwell, Robert M. Califf, Jonas H. Ellenberg. A Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing. New England Journal of Medicine, 2013; 131119084528003 DOI: 10.1056/NEJMoa1310669

Cite This Page:

University of Pennsylvania School of Medicine. "No benefit found to selecting dose of blood thinner based on patients' genetic makeup." ScienceDaily. ScienceDaily, 19 November 2013. <www.sciencedaily.com/releases/2013/11/131119153021.htm>.
University of Pennsylvania School of Medicine. (2013, November 19). No benefit found to selecting dose of blood thinner based on patients' genetic makeup. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2013/11/131119153021.htm
University of Pennsylvania School of Medicine. "No benefit found to selecting dose of blood thinner based on patients' genetic makeup." ScienceDaily. www.sciencedaily.com/releases/2013/11/131119153021.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

EU Ministers and Experts Meet to Discuss Ebola Reponse

EU Ministers and Experts Meet to Discuss Ebola Reponse

AFP (Sep. 15, 2014) The European Commission met on Monday to coordinate aid that the EU can offer to African countries affected by the Ebola outbreak. Duration: 00:58 Video provided by AFP
Powered by NewsLook.com
Despite The Risks, Antibiotics Still Overprescribed For Kids

Despite The Risks, Antibiotics Still Overprescribed For Kids

Newsy (Sep. 15, 2014) A new study finds children are prescribed antibiotics twice as often as is necessary. Video provided by Newsy
Powered by NewsLook.com
FDA Eyes Skin Shocks Used at Mass. School

FDA Eyes Skin Shocks Used at Mass. School

AP (Sep. 15, 2014) The FDA is considering whether to ban devices used by the Judge Rotenberg Educational Center in Canton, Massachusetts, the only place in the country known to use electrical skin shocks as aversive conditioning for aggressive patients. (Sept. 15) Video provided by AP
Powered by NewsLook.com
Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins