Cardiovascular

Warfarin therapy and pharmacogenomics: A step toward personalized medicine

This article is the first in a series that will bring the latest genetic developments from the National Human Genome Research Institute to practicing nurses.

Every day, nurses sit with patients, listen to their concerns, and collaborate with other healthcare team members to tailor treatment to each patient’s physical and psychosocial needs. In short, we try to personalize medicine.

But we know there’s room for improvement. Though we justify our therapeutic choices to ourselves and our patients, many are based on trial and error—an approach that’s inefficient and often dangerous. Take the case of Robert Hayden, age 65, who has a history of hypertension.

About 6 months ago, nursing assessment revealed that Mr. Hayden had an irregular heartbeat. At the time, he didn’t report any cardiac symptoms but said that recently mild exercise was causing dyspnea. Now, he has a stress test for atypical chest pain, and his electrocardiogram reveals atrial fibrillation. He’s referred to the cardiology unit, where 5 mg of warfarin (Coumadin) daily is prescribed. The warfarin clinic monitors his warfarin blood levels and his International Normalized Ratio (INR). On the third day, the clinic tells him to stop warfarin therapy because his INR is 6, an abnormally high value. The clinic reduces his dosage to 2 mg daily, and follow-up testing shows that his INR is 2.4, which is within the therapeutic range.

Discovering genetic variations

Advances in pharmacogenomics, the study of how genetic variation influences drug therapy, are rapidly narrowing the gap between the vision of personalized medicine and the reality. We now know that certain genes (CYP2C9 and VKORC1) affect the metabolism and function of warfarin. That’s in part why some patients need only 1 mg of warfarin daily to maintain a therapeutic blood level, but others need 10 mg daily.


Variants in these genes predispose some patients to adverse drug reactions, specifically bleeding. And genetic testing can now identify patients who will respond to a lower dose of warfarin. Thus, genetic testing results could be used to guide more effective warfarin management and help prevent serious adverse effects.

In August 2007, the U.S. Food and Drug Administration approved updated labeling for warfarin to explain that a person’s genomic make-up may influence how he metabolizes and responds to the drug. The labeling highlights the opportunity for healthcare providers to use genetic tests to prescribe the most reasonable dosage of warfarin for each patient. Today, clinical trials are examining whether genetic testing of a patient’s ability to metabolize warfarin improves outcomes in those needing oral anticoagulation.

Why warfarin?

In the United States, 2 million people a year start taking warfarin to prevent blood clots, heart attacks, and strokes. And, as you know, warfarin has long frustrated healthcare providers, largely because of its narrow therapeutic index, its toxicity, and the variability of patient responses to a given dose.

Patients who take a dose that’s higher than they can tolerate increase the risk of life-threatening bleeding. Patients who take a dose that’s too low increase the risk of dangerous blood clots. Only insulin causes more emergency department visits for adverse drug reactions than warfarin.

 

Not just for drug dosages

In reality, using genetic information to predict how patients will metabolize drugs is just one facet of personalized medicine. Over the next 10 years or so, primary care providers will likely be able to use at least a few drugs that target the molecular consequences of a patient’s disease-causing gene variants. This approach is already used in choosing trastuzumab (Herceptin) for breast cancer therapy.

Also, providers will be able to use genetic testing to screen patients for some adverse reactions to particular drugs. Such screening is available for patients being considered for abacavir (Ziagen) therapy. About 10% of those receiving this antiviral may have a severe hypersensitivity reaction—one that in rare cases, can be fatal. But now, a pharmacogenetic test for the HLA-B*5701 allele can identify patients at risk.

Nursing practice now requires such skills as tailoring genetic and genomic information and services to patients. This increasingly sophisticated form of personalized medicine is here to stay. And this series of articles will help you stay up to date.

Selected references

Consensus Panel on Genetic/Genomic Nursing Competencies. Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics. Silver Spring, MD: American Nurses Association; 2006. www.genome.gov/17517037. Accessed March 7, 2008.

Department of Health and Human Services. Realizing the Promise of Pharmacogenomics: Opportunities and Challenges. Draft report of the Secretary’s Advisory Committee on Genetics, Health, and Society. www4.od.nih.gov/oba/sacghs/SACGHS_PGx_PCdraft.pdf. Accessed March 7, 2008.

Jenkins J, Calzone K. Genomics to health: establishing the essential nursing competencies for genetics and genomics. J Nurs Scholarsh. 2007;39(1):10-16.

Kage B. Medication reactions send 700,000 Americans a year to emergency rooms. Natural News.com. October 18, 2006. www.newstarget.com/020811.html. Accessed March 7, 2008.

Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;7:358(6):568-579.

Dale Halsey Lea is a Health Educator in the Education and Community Involvement Branch and Genomics Healthcare Branch. Greg Feero is Chief of the Genomics Healthcare Branch. Jean F. Jenkins is a Senior Clinical Advisor. All work at the National Human Genome Research Institute, National Institutes of Health, in Bethesda, Md.

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