Pharmacogenomics and heart medications

The field of pharmacogenomics (PGx) is fascinating. Now we can predict not only if drugs will be effective for patients, but also if the drugs are likely to cause significant side effects– even before the patient takes any doses!

You can perform PGx testing at any time. It is best to perform it sooner, rather than later, to experience the full benefit. Since your DNA doesn’t change, the results can benefit you now and for an entire lifetime of future drug therapy decisions! Pre-emptive PGx testing is when we perform the test proactively, with the intent of avoiding ineffective drugs or excessive side effects. Reactive PGx testing is when we wait to perform the test once an issue has occurred. It is still beneficial for patients in both scenarios, regardless of when the test is performed. But it is always better to avoid potential drug issues, whenever possible.

Many drugs used to treat cardiovascular conditions have drug-gene interactions that can dramatically affect drug therapy. This means that your DNA can affect how these drugs behave once they are inside your body. This information is very useful and can greatly impact patient treatment outcomes.

Classes of cardiovascular drugs that can be affected by genetic changes include: cholesterol lowering drugs, blood pressure drugs like beta blockers and calcium channel blockers, heart rhythm drugs, blood thinners, and drugs used for chest pain.

One specific example of a gene which can affect cardiovascular drug therapy is the gene CYP2C19. This gene is responsible for the activation of a drug named Plavix (clopidogrel), which is frequently used in heart attack patients after stent placement. Plavix prevents second heart attacks and strokes by keeping platelets from sticking to each other and to the stent.

Plavix is a “prodrug.” This means that it is a drug in an inactive form that must be activated once inside your body in order for it to produce its desired effect. The gene CYP2C19 is what activates Plavix. In patients who have certain variations in that gene, they won’t be able to activate enough of the drug in order for it to be effective.

So, what happens if a patient with reduced CYP2C19 gene activity takes Plavix? Unfortunately, this means that this patient isn’t likely to form enough active drug to benefit from taking it. There have been case reports of patients experiencing second heart attacks or strokes, or even dying in this scenario1. (You can click the first reference link below to read about a lawsuit involving PGx and Plavix.)

The reason that patients have those terrible problems is because the Plavix wasn’t effective– their platelets stuck to one another and/or to the stent, and caused another blood clot to form. This can lead to catastrophic and debilitating results.

Evidence-based clinical guidelines are available to guide drug therapy decisions for healthcare providers when caring for patients with many known genetic variations2. For this specific situation with Plavix and reduced CYP2C19 activity, these guidelines recommend that alternative drugs such as prasugrel or ticagrelor be used instead of Plavix.

Knowing about such genetic variations in patients can mean the difference between life and death. A simple cheek swab can give us so much information about how our bodies process certain common drugs. It is my passion to help patients and their healthcare providers to access the benefits that PGx has to offer!

References:

 

  1. https://www.reuters.com/article/us-bristol-myers-sanofi-plavix/bristol-myers-sanofi-ordered-to-pay-hawaii-834-million-over-plavix-warning-label-idUSKBN2AF1YI
  2. https://cpicpgx.org/guidelines/

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