Updated December 22, 2021.  

When it comes to cholesterol control, the first line of defence is always a healthy lifestyle and diet. But when that’s not enough, cholesterol medication can help to:

1. Lower the heart-disease-causing bad cholesterol (low-density lipoprotein, LDL),
2. Lower triglycerides, a type of fat in the blood that also increases the risk of cardiovascular problems, and
3. Increase the level of good cholesterol (high-density lipoprotein, HDL), which, conversely, helps fight cardiovascular disease.

While statins are generally safe and effective for many people, there are known genetic factors that influence your risk of developing side effects or the medication being less effective. Understanding your genetic profile can help to reduce these risks.

What are statins?

Statins are medications commonly used to fight high cholesterol. Statins lower cholesterol by directly inhibiting the production of cholesterol in the liver, which accounts for 70% of all cholesterol in your body. The effectiveness and safety of statins and many other medications depend on the genetic makeup of the individual. There are three main genes that code for the enzymes needed to metabolize statins in the liver. These genes are SLCO1B1, ABCG2 and CYP2C9.

Drugs in the statin family include:

What are the risks of taking statins?

Each year in Canada alone, ~200,000 adverse drug reactions occur due to incompatible drug dosages. The most common adverse drug reaction associated with statins is muscle pain and myopathy, which refers to any skeletal muscle weakness. The pain can range from mild discomfort to fatigue or severe pain that impacts daily activities. For example, if you have difficulty getting up from a chair or raising your arms above your head.

Statins are quite important for reducing the risk of heart disease. Despite the side effects, the benefits usually outweigh them. It is, therefore, essential to continue with statins, even in advanced age. A clinical study showed that older adults who stopped taking statins died earlier than individuals that continued treatment.

Genetic factors for statins

Here we explain how genetics-based statin selection and dosing can reduce the risk of side effects and support continued treatment.

Almost all statins are absorbed and distributed in the body by the SLCO1B1 enzyme. Therefore, people with reduced function of this enzyme have greater statin concentration in the blood and more effective cholesterol reduction. However, people with significantly reduced SLCO1B1 function are at higher risk of statin-induced myopathy.

Other enzymes are also crucial for statin metabolism. New clinical guidelines recommend selecting statin and drug dosage depending on a person’s genetic profile.

Rosuvastatin, one of the most prescribed statins, is also impacted by the ABCG2 gene. In addition, the ABCG2 is also involved in the transport of uric acid, which can increase the risk of joint pain for people with reduced function of this enzyme.

Fluvastatin is frequently prescribed for people with muscle or joint pain with other statins because it has a better safety profile. However, the use of fluvastatin with NSAID painkillers (celecoxib, meloxicam), blood thinners such as warfarin, or some antiepileptic medications should be avoided. The risk of side effects is much higher in people with reduced liver enzyme CYP2C9, which is involved in the metabolism of fluvastatin, NSAIDs, warfarin, and phenytoin.

A new clinical guideline recommends genetic testing for SLCO1B1, ABCG2 and CYP2C9 before starting statin treatment and for people who experience statin-induced muscle or joint pain.

How to avoid food and drug interactions with statins

Many antibiotics, heart medications and even certain foods (such as grapefruit) can affect the effectiveness and risk of statin-induced side effects. Such interactions are frequently mediated by the CYP3A4 enzyme, which metabolizes ~50% of drugs, including statins. However, if the CYP3A4 enzyme in your body has a naturally lower metabolic activity, you may experience more substantial side effects.

Many studies have shown that individual variations in the gene that produces CYP3A4 will alter the effectiveness of statin therapy. Furthermore, analysis of hospitalization and medication data of millions of Ontarians highlighted the risk of kidney failure when using statins with macrolide antibiotics. Therefore, statin dosages should be adjusted depending on your natural CYP3A4 activity and other medications you take to ensure maximum safety and efficacy.

Guidelines recommend:

• Increasing statin dosage if your CYP3A4 metabolism is too high or you are on a drug that induces CYP3A4 activity.
• Decreasing statin dosage if your CYP3A4 metabolism is lower than average or another drug is blocking the activity of this enzyme.

Warning: It is important to consult with your doctor or pharmacist before changing the dose of one of your medications or starting a new one.

What other medications are used for high cholesterol?

Most people can continue statin treatment with an adjusted drug dose. Other treatment options include PCSK9 inhibitors alirocumab (Praluent) and evolocumab (Repatha) for a small (2-5%) fraction of the genuinely statin-intolerant population. These drugs are new injectable biological medications, but they are more expensive and not yet covered by some drug plans.

How can you determine the best statin and dose?

The answer to this question is not as complicated as you might think. A painless genetic test by the Pillcheck service will let you know the status of your SLCO1B1, ABCG2, CYP2C9 and CYP3A4 enzymes and predicted response to statins and many other medications. A Pillcheck pharmacist will review your medications along with your DNA profile and help you and your doctor choose the right drugs and dosage for you.

Want to know more about Pillcheck and how it can help you?
Answer a few questions for us here, and we’ll let you know.

References:

Wilke RA et al., The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin Pharmacol Ther. 2012 Jul;92(1):112-7

Magavern EF et al., The role of pharmacogenomics in contemporary cardiovascular therapy: a position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy  Eur Heart J Cardiovasc Pharmacother. 2021 Feb 26;pvab018.

Duarte JD & Cavallari LH Pharmacogenetics to guide cardiovascular drug therapy Nature Reviews Cardiology volume 18, pages 649–665 (2021)

Orkaby AR Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older JAMA. 2020;324(1):68-78. doi:10.1001/jama.2020.7848

Vassy JL et al., Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol: A Randomized Clinical Trial. JAMA Netw Open. 2020 Dec 1;3(12):e2027092.

Mellal AA et al., The clinical significance of statins-macrolides interaction: comprehensive review of in vivo studies, case reports, and population studies Ther Clin Risk Manag. 2019; 15: 921–936.