Statin adverse side effects vs risk of stroke and heart attack: how to balance the risks?

Statins lower LDL cholesterol and reduce the risk of heart attack and stroke. Some studies also link statin use to a lower risk of certain cancers. Statins are among the most prescribed medicines in the world. Yet muscle aches are one of the most common reasons people stop taking them, and stopping a statin can raise cardiovascular risk. Genetic testing can help your doctor choose a statin and a dose with a lower risk of side effects, so you can stay on the treatment you need.

Should you stop your statin because of side effects?

Not on your own. If you have muscle pain or weakness, talk to your doctor or pharmacist before stopping. The Clinical Pharmacogenetics Implementation Consortium (CPIC) states that statin therapy should not be stopped or avoided based on genetic results alone in people who need it. Instead, genetic results can guide which statin and which dose to use.

How common are statin side effects?

Statin-associated muscle symptoms range from mild to serious. According to the 2022 CPIC statin guideline:

• Muscle pain without muscle damage (myalgia) is the most common, affecting about 1 in 10 people.
• Myopathy, where blood tests show muscle damage, affects about 1 in 2,000 people.
• Rhabdomyolysis, severe muscle breakdown that can harm the kidneys, is rare: fewer than 1 in 10,000 people.

The dose matters most. The risk of muscle symptoms is about six times higher on high-dose than on lower-dose statin therapy. Other risk factors include drug interactions, older age, low body weight, female sex, an underactive thyroid, intense exercise, and Asian or African ancestry.

How do your genes affect statin side effects?

Most muscle side effects are linked to how much statin builds up in the blood. Three genes affect this.

SLCO1B1

The SLCO1B1 gene makes a transporter that moves all statins from the blood into the liver, where they work. A common variant (rs4149056, c.521T>C) reduces this transporter's function, so more statin stays in the bloodstream and reaches the muscles. In a landmark study, people with two copies of this variant had about 17 times the risk of myopathy on high-dose (80 mg) simvastatin.

ABCG2

ABCG2 affects how rosuvastatin (Crestor) is absorbed and cleared. People with two copies of a common decreased-function variant (rs2231142) have about 2.4 times the usual rosuvastatin exposure.

CYP2C9

The CYP2C9 enzyme breaks down fluvastatin. Reduced CYP2C9 activity raises fluvastatin levels but does not affect other statins.

What do the guidelines recommend for each statin?

Your test report shows how well your SLCO1B1 gene works: normally, less well ("decreased function") or poorly ("poor function"). If it works normally, any statin can be used as usual. If not, the 2022 CPIC guideline recommends, in simple terms:

Statin	If SLCO1B1 works less well	If SLCO1B1 works poorly
Simvastatin (Zocor)	Another statin is usually better. If it is still used, only a low dose.	Another statin is recommended.
Lovastatin	Another statin is usually better. If it is still used, only a low dose.	Another statin is recommended.
Atorvastatin (Lipitor)	Suitable, starting at a moderate dose.	Suitable, starting at a lower dose.
Rosuvastatin (Crestor)	Suitable at the usual dose. Higher doses need extra care.	Suitable, starting at a lower dose.
Pravastatin	Suitable at the usual dose. Higher doses need extra care.	Suitable, starting at a moderate dose.
Pitavastatin	Suitable, starting at a lower dose.	Suitable, starting at the lowest dose.
Fluvastatin	Suitable at the usual dose. Higher doses need extra care.	Suitable, starting at a moderate dose.

Two other genes fine-tune this advice. If your ABCG2 gene works poorly, rosuvastatin should be started at a lower dose. If your CYP2C9 enzyme is slower than usual, higher doses of fluvastatin should be avoided. Your prescriber chooses the exact statin and dose with you.

For people already taking a statin without problems, CPIC notes it is generally reasonable to continue: after at least 4 weeks without symptoms for moderate-risk combinations, or at least 1 year for high-risk combinations. Your prescriber makes these decisions with you.

Is red yeast rice a safe alternative to statins?

No. Red yeast rice can contain monacolin K, which is structurally identical to the statin lovastatin. Products with significant amounts can cause the same side effects as statins, including muscle, kidney and liver damage, and the same drug interactions. Grapefruit juice is not an alternative either: it can raise blood levels of some statins, such as simvastatin, and increase the risk of side effects.

Can a pharmacogenetic test help?

Pillcheck tests all three genes: SLCO1B1, ABCG2 and CYP2C9. The results help your doctor and pharmacist use CPIC guidelines to choose a statin and dose. Because your genes do not change, the result stays useful for future prescriptions. Learn more in Are Statins Safe? It depends on your genetics! and Should I take statins?

Frequently asked questions

Do statins often cause muscle pain?

About 1 in 10 people taking a statin get muscle pain without muscle damage. Serious muscle damage is rare.

Should I stop my statin if I carry an SLCO1B1 variant?

No. CPIC advises against stopping or avoiding statins based on genetics alone. Talk to your prescriber about which statin and dose suit you.

Which genes affect statin side effects?

SLCO1B1 affects all statins, ABCG2 affects rosuvastatin, and CYP2C9 affects fluvastatin.

Which statin has the lowest risk of muscle side effects?

It depends on your dose and your genes. For people with reduced SLCO1B1 function, CPIC recommends avoiding simvastatin and lovastatin and using lower starting doses of atorvastatin, rosuvastatin, pravastatin or pitavastatin.

Is red yeast rice safer than a statin?

No. It can contain the same compound as lovastatin and cause the same side effects.

References

Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharmacol Ther. 2022;111(5):1007-1021.

SEARCH Collaborative Group. SLCO1B1 variants and statin-induced myopathy: a genomewide study. N Engl J Med. 2008;359(8):789-799.

Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816.

National Center for Complementary and Integrative Health. Red Yeast Rice.