deCODE Complete
Analyzes risk factors for more than fifty common diseases and several traits, including all of those for which deCODEhealth offers individual disease tests. deCODE Complete focuses on medical conditions that can either be better prevented through altered lifestyle or that have better treatment outcomes if detected early. It is the most comprehensive genetic scan available for evaluating risk of common diseases. It is not generally reimbursable.
Diseases and conditions covered by the deCODE Complete Scan:
Abdominal Aortic Aneurysm, ABO Blood Types, Age Related Macular Degeneration, Alcohol Flush Reaction, Alzheimer’s Disease, Asthma, Atrial Fibrillation, Basal Cell Carcinoma, Bitter Taste Perception, Bladder Cancer, Brain Aneurysm, Brain Cancer-Glioma, Breast Cancer, Celiac Disease, Chronic Kidney Disease, Chronic Lymphocytic Leukemia, Chronic Obstructive Pulmonary Disease, Clopidogrel Response, Colorectal Cancer, Crohn’s Disease, Essential Tremor, Exfoliation Glaucoma, Eye Color, Gallstones, Gout, Heart Attack, Hemochromatosis, Hypertension, Kidney Stones, Lactose Intolerance, Lung Cancer, Male Pattern Baldness, Multiple Sclerosis, Nicotine Dependence, Obesity, Ovarian Cancer, Pancreatic Cancer, Peripheral Arterial Disease, Prostate Cancer, Psoriasis, Restless Legs Syndrome, Rheumatoid Arthritis, Statin Induced Myopathy, Systemic Lupus Erythematosus, Testicular Cancer, Thyroid Cancer, Type 1 Diabetes, Type 2 Diabetes, Ulcerative Colitis, Venous Thromboembolism, Warfarin Metabolism.
Clopidogrel Response
Clopidogrel is a “blood-thinning” medication commonly prescribed to help prevent blood clots from forming in small arteries, the clots that can cause a heart attack or stroke.
People respond differently to clopidogrel. Some people carry genetic variations that prevent clopidogrel from being converted into its active clot-preventing form in the body.
These genetic variations result in decreased clopidogrel response and therefore reduced protection from heart attacks, strokes and death from these causes.
People´s blood clotting response to clopidogrel varies. deCODEhealth may help determine the best blood-thinning strategy.
Blood clotting is a normal and necessary defense mechanism
Normally, when a small blood vessel is ruptured or damaged, a blood clot forms to plug the hole until the blood vessel heals. Small cells in the blood called platelets make the blood clot. When a platelet detects a damaged area of a blood vessel, it produces a chemical that attracts other platelets and makes them stick together to form a blood clot. This aggregation, or clumping, is one of the early steps in producing a blood clot, a beneficial effect under ordinary circumstances.
Clopidogrel prevents blood clot formation
In most cases, a heart attack or stroke is caused by a blood clot that reduces or blocks the flow of blood through an artery. Clopidogrel (which has several brand names including Plavix®, Clopilet®, Ceruvin®, and Iscover®) prevents platelets in the blood from sticking together and forming blood clots. Clopidogrel is therefore referred to as a “blood thinner” and is commonly prescribed for people who have had a heart attack or undergone coronary artery stent placement to help protect them from future heart attacks or strokes.
Clopidogrel is ofen prescribed with, or instead of, aspirin
Aspirin is another commonly used “blood-thinning” medication. Although aspirin and clopidogrel both affect aggregation of platelets in the blood, they act through different mechanisms. Doctors often prescribe clopidogrel and aspirin together to achieve stronger blood clotting prevention than is possible with either drug alone. Clopidogrel is also used when people cannot use aspirin, for example due to gastric side-effects or aspirin resistance.
Clopidogrel is activated by the CYP2C19 gene
Clopidogrel is ingested as a so-called inactive pro-drug. It must be metabolized or broken down by certain enzymes to produce the active drug that inhibits platelet aggregation. This is predominantly done by an enzyme called cytochrome P-450 2C19, which is encoded by the CYP2C19 gene. Many variants have been identified in this gene that lead to decreased function of the resulting enzyme and therefore less efficient conversion of clopidogrel to its’ active form. Several studies have shown that the anti-platelet effect of clopidogrel is decreased in individuals with decreased CYP2C19 enzymatic activity.
Some people have a decreased response to clopidogrel
Although the benefits of clopidogrel in treatment and prevention in cardiovascular disease are well established, not all individuals respond in the same way to clopidogrel. There are individuals who develop blood clots and suffer heart attack or stroke despite clopidogrel treatment. Studies have identified genetic variants in the CYP2C19 gene, referred to as CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*8 and CYP2C19*17, that are associated with variability in clopidogrel response. The frequency of these variants varies considerably by population, for example approximately 50% of Chinese, 34% of African Americans, 25% of white people of European ancestry, and 19% of Mexican Americans carry at least 1 copy of the CYP2C19*2 variant that reduces enzymatic function.
Knowing your patients’ CYP2C19 status may help determine the best blood-thinning strategy.
deCODEhealth calculates your patients’ risk for decreased clopidogrel response
The deCODE Complete Scan identifies five genetic variants in the CYP2C19 gene on chromosome 10, ( CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*8, and CYP2C19*17 ), and uses them to provide customers of various populations with a personalized interpretation of their genetic risk for decreased response to clopidogrel.
Please note that these variants only provide information about your patients’ genetic propensity in relation to the blood clotting effects of clopidogrel.
Many other factors can affect their actual clopidogrel response. It is essential that any decisions about clopidogrel therapy and dose size be taken in consultation with a physician.
Other causes of decreased clopidogrel response
In November, 2009, the U.S. Food and Drug Administration notified health professionals of an interaction between clopidogrel and omeprazole (with the brand name Prilosec®), a drug used to reduce stomach acid. New data show that when clopidogrel and omeprazole are taken together, the effectiveness of clopidogrel is reduced.
People taking clopidogrel to reduce the risk of heart attacks or strokes are unlikely to experience the the full effect of this medication if they are also taking omeprazole.
Other drugs that are expected to have a similar effect and should be avoided in combination with clopidogrel include: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine.
More information
For more information about clopidrogel response we recommend talking to your doctor and visiting the following websites:
- Anti-platelet medications – from The American Heart Association
- Clopidogrel – from MedlinePlus, Trusted Health Information for You
- Clopidogrel Patient Information – from MedlinePlus, Trusted Health Information for You
- Plavix (clopidogrel) patient information – from the UK´s National Health System
- Frequently asked questions about Plavix – from WebMD
Scientific references
- Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet. 2006 Feb 18;367(9510):606-17.
- Holmes DR Jr, Dehmer GJ, Kaul S, et al. ACCF/AHA clopidogrel clinical alert: approaches to the FDA boxed warning: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Journal of the American College of Cardiology. 2010 Jul 20;56(4):321-41.
- Mega JL, Close SL, Wiviott SD et al. Cytochrome p-450 polymorphisms and response to clopidogrel. The New England Journal of Medicine. 2009 Jan 22;360(4):354-62. Epub 2008 Dec 22.
- Simon T, Verstuyft C, Mary-Krause M, et al. Genetic Determinants of Response to Clopidogrel and Cardiovascular Events. The New England Journal of Medicine. 2009 Jan 22;360(4):363-75. Epub 2008 Dec 22.
This content was last reviewed on February 23, 2011.