Statins are one of the biggest advances in modern therapeutics. Statins have a clear effect of preventing cardiovascular disease and prolonging life, making them one of the most prescribed drugs. Statins are very well tolerated, but there are some patients who cannot tolerate statins. In addition, some patients are concerned that statins may cause diabetes, cancer, and memory loss and often ask whether they need to continue taking the medication. This article explores statin intolerance to help patients better understand the benefits and risks of statins. What are the benefits of statins? Statins (e.g., atorvastatin [Lipitor], resupristatin [Codine], simvastatin [Sulforaphane], etc.) work by inhibiting the synthesis of cholesterol in the liver, thereby lowering cholesterol in the blood. In particular, they lower low-density lipoprotein cholesterol (LDL-C, commonly known as “bad cholesterol”), thereby reducing the incidence of myocardial infarction and stroke and extending life expectancy. In a large analysis of more than 170,000 patients, each 1.0 mmol/L reduction in LDL-C was associated with a reduction in the incidence of serious cardiovascular events by approximately one quarter (20-25%) and an increase in life expectancy. Importantly, the lower the LDL-C reduction, the greater the cardiovascular protective effect. Even for low-risk patients, the cardiovascular benefit of statins far outweighs the risk of side effects. For this reason, clinical guidelines around the world strongly recommend statins for patients with cardiovascular risk disease and emphasize the use of potent statins with an effect sufficient to reduce LDL-C by 50%. What is statin intolerance? As the term implies, statin intolerance means that a patient is unable to continue a statin, either because of side effects or because of a certain level of abnormalities in blood tests for liver or muscle function. Intolerance can be classified as partial intolerance (certain statins at certain doses) or complete intolerance (any statin at any dose). The most common manifestation of statin intolerance is muscle pain, weakness, and cramping, which can be seen in 15% of patients. In most cases, symptoms are mild, with rare myositis and elevated muscle damage markers. Once the statin is discontinued, symptoms resolve within a short period of time. Severe muscle damage or rhabdomyolysis is very rare, occurring in only 1 in 23 million patients on atorvastatin. Mild to moderate elevation of creatine kinase without other muscle-related side effects can sometimes occur, and statin therapy should not be discontinued at this time. The muscle side effects of statin may be related to the effect of statin on energy metabolism and the decrease in intramuscular coenzyme Q10 levels. What are the risk factors for statin intolerance? Endogenous: advanced age (>80 years), female, Asian, family history of neuromuscular disease, myopathy or disease syndrome, liver disease, renal disease, untreated hypothyroidism, rare genetic polymorphisms regulating hepatic cytochrome enzymes. External causes: high doses of statins, alcohol abuse, drug interactions (gefirozil, antipsychotics, amiodarone, verapamil, cyclosporine, macrolide antibiotics, imidazole antifungals, protease inhibitors), strenuous exercise, heavy consumption of grapefruit juice. What are the other side effects of statins? Statins are well tolerated and the risk of serious side effects is very low. However, because statins are so widely used, they are often blamed for certain symptoms when they occur. However, data from up to 20 years of follow-up suggest that long-term use does not increase serious adverse effects. Adverse effects for which there is definite evidence include: myopathy (muscle pain/spasm, myositis, rhabdomyolysis), increased liver enzymes, and new-onset diabetes mellitus. Adverse reactions for which evidence was lacking were: cancer, intracranial hemorrhage (hemorrhagic stroke), cognitive decline (Alzheimer’s disease), pulmonary disease, sexual dysfunction, fatigue, headache or dizziness, psychological disorders, cataracts, rheumatoid arthritis, gastrointestinal discomfort, abdominal pain, permanent liver and kidney damage. Liver enzymes may exceed the normal range in 0.1% to 3% of people on high doses of statins, but they recover once the drug is discontinued, and permanent liver damage is rare (<1 in 2 million). Recently, statin application has been found to be associated with new-onset diabetes mellitus. However, this risk is very small and is not comparable to the benefit of statins. Statin therapy increases diabetes by 1 case for every 255 patients treated for 4 years, but prevents at least 5 serious cardiovascular events (myocardial infarction or stroke). What if I can't tolerate a statin? First, the reduction in myocardial infarction and stroke associated with statins is not achieved with other drugs or dietary regimens. If statin intolerance is suspected, try stopping the drug for a short period of time and then try the statin again. You can try different doses, different types of statins or intermittent dosing, which can sometimes work. Current studies do not support the application of vitamins and minerals (e.g., coenzyme Q10) to reduce statin side effects. Also, reversible causes, such as drug interactions and hypothyroidism, should be excluded. If it is true that statins cannot be applied, then they can only be replaced by other drugs, but other drugs cannot achieve the cardiovascular protective effect of statins. A new drug currently under investigation, PCSK9 inhibitor, can significantly reduce LDL-C (up to 60% or more) and is likely to be available in a few years. However, its cardiovascular protective effects and side effects of long-term application have not been elucidated.