Atorvastatin and Pharmacogenomics: Personalising Heart Health

Published 02/05/2025

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A Close Look at Atorvastatin

Atorvastatin is one of the most commonly prescribed medications in the UK for managing high cholesterol and reducing cardiovascular risk. But beyond its well-known cholesterol-lowering effects, atorvastatin has a range of additional benefits—and potential side effects—that are influenced by your unique genetic profile. Thanks to advances in pharmacogenomics in the UK, it’s now possible to understand how your genes affect your response to medications like atorvastatin, allowing for a safer, more effective, and more personalised medicine approach.

Introduction to Atorvastatin

Atorvastatin belongs to the statin family, originally developed from natural compounds produced by fungi. These compounds were discovered to inhibit cholesterol synthesis in microbes, a mechanism later adapted to reduce cholesterol in humans.

Like other statins, atorvastatin has been found to have pleiotropic effects—benefits beyond lowering cholesterol. These include anti-inflammatory properties, improved blood vessel function, and plaque stabilisation. At the same time, some patients experience side effects, most notably muscle-related symptoms. Understanding who is most at risk is a key part of personalised medicine for statins.

Why Atorvastatin Is Prescribed

Atorvastatin may be prescribed for several reasons (5):

High cholesterol levels not adequately controlled by lifestyle changes
Primary prevention in people at high risk of heart disease or stroke
Secondary prevention following a heart attack or stroke (widely supported by evidence, though unlicensed for this use in some regions)

How and When to Take Atorvastatin

The usual starting dose is 10 mg once daily, usually taken at the same time each day. The dose may be increased to 40 mg, with adjustments made at intervals no shorter than 4 weeks. The maximum recommended dose is 80 mg per day (5).

Unlike simvastatin, which is short-acting and typically taken at night, atorvastatin has a longer half-life, so timing is more flexible. However, consistency is key to maintaining stable levels in the bloodstream.

Atorvastatin Side Effects

While atorvastatin is generally well tolerated, it can cause side effects in some individuals. Being aware of these helps patients know when to seek advice.

Muscle-Related Side Effects

Atorvastatin is a lipophilic statin, meaning it penetrates tissues like muscle and brain more easily. This contributes to its effectiveness—but also raises the chance of muscle-related side effects, such as:

Muscle pain, soreness, or tenderness (especially if unrelated to exercise or infection)
Symptoms most often appear in the thighs, calves, or hip flexors
Occurs in approximately 10–29% of patients and is the leading cause of statin discontinuation (6)

Other Possible Side Effects

Painful joints
Fatigue or weakness
Dizziness
Sleep problems
Memory changes (especially at higher doses)
Liver enzyme abnormalities

If you experience side effects, especially muscle symptoms, it may be worth considering pharmacogenetic testing for statins.

Who Is Most at Risk?

Certain factors increase the risk of statin-related muscle symptoms (11):

Age over 60
Diabetes
Hypothyroidism
Vitamin D deficiency
High levels of physical activity
Alcohol use
Major surgery
Higher statin doses (strongest risk factor)

How Your Genes Influence Atorvastatin's Efficacy

Atorvastatin’s journey through your system—how it’s absorbed, distributed, metabolised, and eliminated—is governed by both biological and genetic factors. These areas are known as pharmacokinetics and pharmacogenetics (10).

Absorption & Distribution: As a lipophilic drug, atorvastatin is rapidly absorbed in the gut and taken up into liver cells via OATP1B1, which is encoded by the SLCO1B1 gene.
Metabolism: Atorvastatin is extensively metabolised in the gut and liver, primarily by CYP3A4 and CYP3A5 enzymes. Active metabolites account for around 70% of its activity.
Elimination: Most atorvastatin is eliminated via the bile and faeces, using transporters like P-glycoprotein (P-gp) and BCRP.

These pathways are all influenced by genetic variations, making genetic testing for statin response a useful tool for personalising care.

Personalising Atorvastatin with Pharmacogenetics

One of the most important genes affecting statin response is SLCO1B1:

This gene encodes the OATP1B1 transporter, which helps statins enter liver cells
Reduced transporter function (e.g. the c.521T>C variant, rs4149056) raises systemic statin levels, increasing side effect risk
People with two copies of the C allele (C/C) have a much higher risk of statin-induced myopathy

These insights help explain why some people tolerate atorvastatin well, while others experience side effects—even at standard doses. Pharmacogenomics UK services now make it easier to identify these differences and personalise prescribing.

Could a Genetic Test Help?

Understanding your individual risk of side effects—especially from statins like atorvastatin—can be challenging. A pharmacogenomics (PGx) test in the UK can help identify how your genes influence your response to medications like atorvastatin, supporting safer, more personalised medicine through genetic testing for medication response. In some cases, PGx tests are available through the NHS, however if this isn't a option, they can be ordered privately or from our consumer website.

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