Are Statins Safe? It depends on your genetics!

Ruslan Dorfman, PhD, MBA15 Oct 2026

When it comes to cholesterol, the first line of defence is always a healthy lifestyle and diet. When that is not enough, statins are the most widely used and best-studied cholesterol medications. Their main job is to lower "bad" cholesterol (low-density lipoprotein, LDL), which builds up in the arteries and causes heart attacks and strokes. Statins also lower triglycerides slightly. Statins are safe and effective for most people, and studies suggest they may also reduce the risk of some cancers. Still, genes and other medications can raise the risk of side effects or make a statin less suitable for some people. Knowing your genetic profile can help reduce these risks.

What are statins?

Statins lower cholesterol by blocking an enzyme the liver needs to make cholesterol. The liver makes most of the cholesterol in the body, so when production drops, the liver pulls more LDL cholesterol out of the blood. The statins available in Canada are:

Atorvastatin (Lipitor)
Rosuvastatin (Crestor)
Simvastatin (Zocor)
Pravastatin
Lovastatin
Fluvastatin (Lescol)
Pitavastatin (Livalo)

Are statins safe?

For most people, yes. The most common complaint is muscle pain or weakness, which can range from mild aches to pain that makes it hard to get up from a chair or lift your arms. However, a 2022 analysis of 23 large blinded trials found that statins cause only a small, mostly mild increase in muscle symptoms, mainly in the first year. More than 90% of the muscle complaints reported by people taking statins were not caused by the statin. Serious muscle damage (rhabdomyolysis) is rare.

The benefits of statins usually far outweigh the risks. In a large study of US veterans aged 75 and older, statin use was linked with lower overall and cardiovascular death rates. Before stopping a statin because of side effects, talk to your health care provider. For more, read Statin side effects vs risk of stroke and heart attack.

Which genes affect statin safety?

The CPIC 2022 statin guideline covers three genes:

Gene	What it does	Statins affected	What reduced function means
SLCO1B1	A transporter that carries statins from the blood into the liver, where they work	All statins, most strongly simvastatin and lovastatin	More statin stays in the blood and reaches the muscles, raising the risk of muscle side effects
ABCG2	A transporter that affects how rosuvastatin is absorbed and cleared	Rosuvastatin	Higher rosuvastatin levels; a lower starting dose may be needed
CYP2C9	A liver enzyme that breaks down fluvastatin	Fluvastatin	Higher fluvastatin levels; the dose should be limited or another statin chosen

Based on these genes, the guideline recommends which statin to choose and at what starting dose. For example, people with poor SLCO1B1 function should avoid simvastatin and lovastatin and start other statins at a lower dose. Statin-by-statin recommendations are in our article on statin side effects. In a randomized trial, giving doctors SLCO1B1 results led them to avoid simvastatin in people at genetic risk, without making cholesterol control worse.

Reduced ABCG2 function also raises uric acid levels and is linked to gout. This is separate from statin side effects, but it is useful to know if you have joint pain.

How do other drugs and foods interact with statins?

Many drug interactions with statins go through the liver enzyme CYP3A4, which breaks down about half of all medications, including simvastatin, lovastatin and atorvastatin. Drugs and foods that block CYP3A4 can raise the levels of these statins and the risk of muscle damage. Examples include:

The antibiotics clarithromycin and erythromycin (but not azithromycin)
Some antifungals, such as itraconazole and ketoconazole
Some HIV and hepatitis C medications
Some heart medications, such as diltiazem, verapamil, amiodarone and amlodipine
Large amounts of grapefruit juice

In an Ontario study of more than 140,000 older adults taking statins, those prescribed clarithromycin or erythromycin had a higher risk of hospitalization for acute kidney injury and muscle damage, and a higher risk of death, than those prescribed azithromycin. Drugs that speed up CYP3A4, such as rifampin, carbamazepine and St. John's wort, can lower statin levels and make them less effective.

Rosuvastatin, pravastatin and pitavastatin are not significantly broken down by CYP3A4, so they are often chosen when interactions are a concern. Some interactions go through other pathways: cyclosporine and gemfibrozil raise the levels of most statins by blocking the SLCO1B1 transporter.

The CYP3A4 gene itself also varies between people, and some variants have been linked to how much statin a person needs. There are no genetic dosing guidelines for CYP3A4 yet, but knowing your CYP3A4 status together with your other medications helps a pharmacist spot interactions.

Warning: always talk to your doctor or pharmacist before changing the dose of a medication or starting a new one.

Illustration of how pharmacogenetics helps find the right medication dose for different people

What if a statin is not suitable for you?

Most people who have side effects can continue a statin by switching to another statin or lowering the dose. According to the 2021 Canadian Cardiovascular Society guidelines, other options to lower LDL cholesterol include:

Ezetimibe, a tablet that reduces cholesterol absorption from food, usually the first add-on.
PCSK9 inhibitors, alirocumab (Praluent) and evolocumab (Repatha), injections every two to four weeks.
Bempedoic acid (Nexletol), a tablet that works in the liver and rarely causes muscle symptoms.
Inclisiran (Leqvio), an injection given twice a year after the first doses.

Some of these newer drugs are more expensive and are not covered by all drug plans.

How can you find the best statin and dose for you?

A painless genetic test by Pillcheck reports your SLCO1B1, ABCG2, CYP2C9 and CYP3A4 status and your predicted response to statins and many other medications. A Pillcheck pharmacist reviews your medications together with your DNA profile and helps you and your doctor choose the right statin and dose.

Frequently asked questions

Are statins safe to take long term?

For most people, yes. Large trials show that serious side effects are rare and that the benefits for the heart and blood vessels outweigh the risks.

Which gene affects statin side effects the most?

SLCO1B1. People with reduced SLCO1B1 function have higher statin levels in the blood and a higher risk of muscle side effects, especially with simvastatin.

Can I eat grapefruit while taking a statin?

Large amounts of grapefruit juice can raise the levels of simvastatin, lovastatin and atorvastatin by blocking CYP3A4. Rosuvastatin and pravastatin are not significantly affected. Ask your pharmacist about your statin.

Which antibiotics should be avoided with statins?

Clarithromycin and erythromycin block CYP3A4 and can raise the levels of simvastatin, lovastatin and atorvastatin. Azithromycin does not have this effect. Tell your prescriber you take a statin before starting an antibiotic.