Cardiovascular PGx Test Panel
Test Description
The Cardiovascular PGx Test Panel is intended for individuals receiving cardiovascular therapies who may benefit from personalized pharmacogenetic-guided medication management. This panel evaluates clinically relevant genetic variants associated with drug metabolism, efficacy, and bleeding or clotting risk for commonly prescribed anticoagulant and antiplatelet medications, including warfarin, clopidogrel, ticagrelor, prasugrel, and acenocoumarol. Pharmacogenetic testing may help guide medication selection and dosing, improve therapeutic safety and effectiveness, reduce the risk of adverse drug reactions, and support individualized cardiovascular treatment strategies. Upon completion of testing, patients receive an interpretive pharmacogenetic report and certificate summarizing clinically relevant results and medication-related findings to support ongoing care and future treatment decisions.
Ordering Information
Turnaround Time: 3-7 business days
Preferred specimens: Saliva
Alternate specimens: Buccal Swab
Clinical Description
Many of cardiovascular medications are metabolized by certain cytochromes in liver. The exact same dose of a medication can produce different results in different individuals. This inter-individual variability can be due to genetic of such cytochromes or other genetic pathways. If someone has increased activity of these cytochromes, the drugs may be eliminated from body more quickly resulting in decreased efficacy. If someone has decreased activity of these cytochromes, the drugs may be built up in body resulting in toxicity. Therefore, determining the genetic make-up of an individual can help with precision prescribing of the medications.
Clopidogrel is a prodrug which needs to be activated by a cytochrome called CYP2C19. According to American College of Cardiology Foundation/American Heart Association Acute Coronary Syndrome (ACS) guidelines, genetic testing for CYP2C19 loss-of-function alleles should be considered on a case-by-case basis, especially in individuals with recurrent ACS while receiving treatment with clopidogrel.
“Error and trial approach” in case of a life-threatening condition such as acute coronary event especially may not be advisable.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline recommends using an alternative agent in patients with at least one decreased function allele due to risk for decreased response. Patients with genotype of increased metabolism should be monitored for increased bleeding risk.
Warfarin, a vitamin K antagonist is a commonly used anticoagulation medication with significant inter-individual variability and narrow therapeutic index leading to frequent complications due to over and under dosing. Genetic variants in CYP2C9, CYP4F2 and vitamin K epoxide reductase complex subunit 1 (VKORC1) can predict the dose needed to meet the therapeutic level.
Statins
Concomitant use of statins such as simvastatin with certain drugs may lead to increased blood concentration of simvastatin resulting in myotoxicity. An alternative agent or a reduced dose of simvastatin should be prescribed to patients with at least one reduced function allele in SLCO1B1.
Anticoagulants and Antiplatelet Agents (Blood Thinners)
| Medication | Gene |
| Warfarin* | VKORC1, CYP2C9, CYP4F2 |
| Clopidogrel | CYP2C19 |
| Ticagrelor | CYP3A4, CYP3A5 |
| Prasugrel | CYP2C19 |
| Acenocoumarol | CYP2C9 |
*CPIC guideline pharmacogenetic algorithm https://cpicpgx.org/content/guideline/publication/warfarin/2017/28198005.pdf
Hyperlipidemia (High Blood Cholesterol)
| Medication | Gene |
| Simvastatin, Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin | SLCO1B1, CYP2C9, ABCG2 |
| Atorvastatin | CYP3A4 |
Frequency of Cytochrome P450 (CYP2D6, CYP2C9, CYP2C19) Metabolizer Types in the population
| Cytochrome | Poor metabolizer | Intermediate metabolizer | Normal metabolizer | Rapid or ultra-rapid metabolizer |
| CYP2D6 | 4-7% | 9-35% | 50-90% | 2-3% |
| CYP2C9 | 3% | 30% | 68% | N/A |
| CYP2C19 | 2-20% | 24-36% | 14-44% | 30% |
Hypertension (High Blood Pressure)
| Medication | Gene |
| Beta Blockers (Carvedilol, Timolol, Metoprolol, Propranolol, Nebivolol) | CYP2D6 |
| Clonidine | ADRA2A |
Antiarrhythmics (Irregular Heart Rhythm)
| Medication | Gene |
| Flecainide, Propafenone, Ranolazine | CYP2D6 |
General Cardiac
| Condition | Gene |
| Thrombosis | FII, FV, MTHFR |
Tagged Genes
- Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–549.
- Johnson JA, Cavallari LH. Pharmacogenetics and cardiovascular disease: implications for personalized medicine. Pharmacol Rev. 2013;65(3):987–1009.
- Cavallari LH, Lee CR, Beitelshees AL, et al. Multisite investigation of outcomes with implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. JACC Cardiovasc Interv. 2018;11(2):181–191. doi:10.1016/j.jcin.2017.07.022
- Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non–ST-elevation myocardial infarction. Circulation. 2012;126(7):875–910. doi:10.1161/CIR.0b013e318256f1e0
- Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94(3):317–323. doi:10.1038/clpt.2013.105
- Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017.
- Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376(9753):1658–1669. doi:10.1016/S0140-6736(10)60310-8
- The SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med. 2008;359(8):789–799. doi:10.1056/NEJMoa0801936
- Clinical Pharmacogenetics Implementation Consortium (CPIC). Genes–drug pairs.
- U.S. Food and Drug Administration. Table of pharmacogenomic biomarkers in drug labeling.
