While COVID-19 rightly remains the focus of national healthcare news, heart disease is still the leading cause of death. Your patients with cardiovascular diseases — especially heart failure, coronary artery disease, cardiomyopathies, and pulmonary hypertension — may also be at greater risk of severe illness if infected with COVID-19, compounding the risks of both.
February is American Heart Month, and we know you’re already doing so much to guide your patients toward better heart health while managing any chronic cardiovascular conditions. You’re recommending lifestyle and diet changes for heart healthy living. You’re ordering screening and diagnostic tests to evaluate the current state of their heart health. And for many, you’re addressing underlying heart conditions by prescribing medications: antihypertensives, antianginals, antiarrhythmics, anticoagulants, antiplatelets, beta blockers, diuretics, and statins.
As you well know, every patient responds a little differently to these medications. Choosing the right medicine and optimal dosage for each patient usually requires some trial and error, sometimes with the risk of adverse reactions. For a patient with serious cardiovascular disease, that’s lost time during which more damage may be done, and the potential for lasting harm from adverse drug events.
Taking the Guesswork Out of Heart Medicines
Pharmacogenomic testing uses genotyping to detect single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in several drug metabolizing enzyme (DME) genes. In the case of cardiovascular medicines, we look for SNPs and CNVs that impact how a patient will metabolize these medicines. You can then use that information to select the most effective medicine and dosage for your patient, while avoiding adverse reactions.
“In the case of clopidogrel, warfarin, and statins, the literature has become sufficiently strong that guidelines are now available describing the use of genetic information to guide treatment with these therapies,” according to a report in Pharmacological Reviews, “and some health centers are using this information in the care of their patients.”
For example, as you know, the anticoagulant warfarin requires a careful balancing act in dosing. Too little, and the patient remains at risk of blood clots. Too much, and they risk uncontrolled bleeding. The traditional trial and error approach attempts to thread the needle between these risks.
However, much of the variation in individual response to warfarin can be predicted by two SNPs. CYP2C9 encodes the enzyme that metabolises warfarin. And VKORC1 provides a reductase for vitamin K, which limits the impact of warfarin. In one study, patients with both variant alleles “required a 15% to 30% lower maintenance dose to maintain stable blood levels.” If given a standard dose, these patients would be at greater risk of uncontrolled bleeding. Another study found that about 35% of the population required different dosing because of these variations.
Identifying Slow Metabolizers and Ultrarapid Metabolizers
Many of the variations identified by pharmacogenomic testing come down to the production of enzymes that metabolize drugs. Recommended dosage of medicines is generally based on the metabolism of “extensive metabolizers.” Slow and intermediate metabolizers of a given drug may experience more severe side effects and have a less effective therapeutic response. Ultrarapid metabolizers may metabolize the drug too quickly, making it difficult to maintain optimal levels in the body.
The CYP2D6 gene, for example, is responsible for the metabolism of antianginal agents such as ranolazine; antiarrhythmics such as flecainide, mexiletine, and propafenone; and beta blockers such as carvedilol, metoprolol, nebivolol, propranolol, and timolol. Patients with variations of CYP2DC may need an altered dosage or dose frequency of these medicines to reduce side effects and improve therapeutic efficacy.
The antiplatelet drug clopidogrel is metabolized by an enzyme coded by CYP2C19. Carriers of a CYP2C19 variation may metabolize clopidogrel more slowly and not receive the full therapeutic benefit. Carriers of a different variation are ultrarapid metabolizers of clopidogrel and more likely to respond well to the drug.
One more example: a significant minority of patients prescribed statins to lower cholesterol experience neuromuscular pain. One study linked this to an allele of the SLCO1B1 gene, which encodes a protein that removes statins from the blood. Variations of SLCO1B1 may inhibit removal of statins, leading to greater toxicity and neuromuscular pain.
As Genetic Science Advances, Pre-Emptive Pharmacogenomics Should Follow
While some links from SNPs and CNVs to heart medicine efficacy and side effects are stronger than others, new studies come out regularly, each moving us a little closer to truly personalized medicine. Where the science is strong, testing for these genetic variations should become standard practice in the clinical setting.
“Genetic tests that are available should be used to determine the proper drug and the dosage alteration needed for an individual patient as much as possible,” according to a report on pharmacogenomics in the journal Nursing.
The same report addresses the ethical concerns some doctors and patients may have with genetic testing: “Ethical concerns may arise about these tests, but unlike disease-based genetic tests, these assays look at specific markers associated with drug metabolism.”
These tests should often be administered prior to initial prescription, not only when a standard prescription produces adverse effects. A report in the journal Circulation, a publication of the American Heart Association, found “genetic factors play a prominent role in 20% to 30% of cases” of serious adverse events when prescribing cardiovascular medicines. In some cases, pre-emptive pharmacogenomics can identify these risks prior to prescribing.
According to a study in the journal Genetics in Medicine, “pre-emptive testing has potential to improve patient satisfaction and generate significant reductions in the utilization of reactive genetic testing.”
Pharmacogenomic Testing for Cardiovascular Medications
Here at LifeBrite Labs, we’re doing our part to support you in providing truly personalized medicine to your heart patients. During American Heart Month and all year long, our cardiovascular medications pharmacogenomics panel empowers you with the information you need to select the most appropriate medicine and dosage for each individual.
Contact us anytime if you’d like to learn more about all our pharmacogenomics panels, which include panels for medication used in the treatment of cancer, diabetes and gastrointestinal diseases, immunology and urology, infectious diseases, pain, and psychotropics.
Atlanta-based LifeBrite, led by CEO Christian Fletcher, operates LifeBrite Laboratories, LifeBrite Community Hospital of Stokes, and LifeBrite Community Hospital of Early.