Heart Medications: One Size Does Not Fit All

Cardiovascular disease is the leading cause of death globally, responsible for roughly a third of all deaths. Cardiovascular drugs are among the most widely prescribed medicines in the world — and like all medicines, they can cause unwanted effects or simply fail to work as intended in a given person.

Traditionally, prescribers have worked on a broadly "one size fits all" basis, adjusting by trial and error. Pharmacogenomics — the study of how your genes affect your response to medication — is beginning to change that.

Why people respond differently

Each of us carries a unique genetic code, and part of that code determines how efficiently we produce the enzymes that activate, metabolise and clear medicines. Variation in those enzymes means the same dose of the same drug can produce very different blood levels, and very different effects, in two people of the same age and weight.

Clopidogrel and CYP2C19

Clopidogrel is an antiplatelet medicine widely prescribed after heart attacks, stents and strokes. It is a prodrug — it must be converted into its active form by an enzyme produced by the CYP2C19 gene.

People who carry loss-of-function variants in CYP2C19 convert less of the drug and so get less antiplatelet effect — leaving them at higher risk of a further cardiovascular event despite taking their medication correctly. Depending on ancestry, a significant minority of people are affected. Where testing identifies a poor metaboliser, an alternative antiplatelet such as prasugrel or ticagrelor may be more appropriate. Some cardiology services now test routinely after stenting.

Warfarin, CYP2C9 and VKORC1

Warfarin is an anticoagulant used to prevent strokes and treat clots. Its therapeutic window is narrow: too little offers no protection, too much causes dangerous bleeding. The required dose varies enormously between individuals — by more than tenfold.

Two genes explain much of that variation. CYP2C9 affects how quickly warfarin is broken down, and VKORC1 affects the sensitivity of warfarin's target. Certain combinations make a person highly sensitive, requiring a much lower starting dose to avoid bleeding.

In practice, UK use of warfarin has fallen considerably as direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban have become first-line for many indications — they need no routine monitoring and have fewer dietary interactions. Warfarin remains essential for some patients, particularly those with mechanical heart valves.

Statins and SLCO1B1

Statins lower cholesterol and are among the most prescribed medicines in the UK. A minority of people experience muscle aches on them. Variants in the SLCO1B1 gene, which governs how simvastatin is transported into the liver, are associated with higher blood levels and an increased likelihood of muscle-related side effects — information that can guide the choice of statin or dose.

What this means in practice

Pharmacogenomic testing can help:

• Identify people unlikely to respond well to a particular drug before it fails them
• Guide starting doses where the therapeutic window is narrow
• Reduce avoidable side effects and hospital admissions
• Shorten the trial-and-error period when starting treatment
• Give relatives useful information, since these variants run in families

Important limitations

Genetics is one input among many. Age, kidney and liver function, other medications, diet, smoking and adherence all affect drug response, often more than genotype does. Pharmacogenomic testing is currently used selectively in the NHS rather than universally, and the evidence base is stronger for some drug–gene pairs than others.

Most importantly: never stop, start or change the dose of a cardiovascular medicine on the basis of a genetic result alone. Abruptly stopping an antiplatelet, anticoagulant or beta-blocker can be dangerous. Any change belongs with the clinician who prescribes it.

Pharmacogenetic testing with Rightangled

Rightangled's DNA tests examine genetic markers relevant to cardiovascular health and medication response. Results are reviewed by our clinical team, which includes GPhC-registered independent prescribers, with medical oversight from our doctor, Dr Abdullah — giving you a clear explanation of your result and what is worth raising with your own prescriber.

Verify us with the General Pharmaceutical Council (registration 9011933), see our LegitScript certification, and read reviews on Trustpilot.

Related reading: genetic influence on beta-blocker therapy.

This article is for general information and does not replace personalised medical advice. Never change prescribed medication without speaking to your clinician.