More and more people are taking statins to combat hypercholesterolemia, mixed hyperlipidemia, and atherosclerotic cardiovascular disease (ASCVD). Its specific role is lipid regulation, anti-inflammatory, improving vascular endothelial function, and stabilizing atheroplaque.
Atherosclerotic cardiovascular disease (ASCVD) is more common in people over the age of 60. ● Coronary heart disease, manifested by fatal or non-fatal myocardial infarction and angina. ● Cerebrovascular disease, fatal or non-fatal stroke and transient ischemic attack● Peripheral arterial disease, manifested by intermittent claudication and severe limb ischemia● Aortic atherosclerosis and thorcotic/abdominal aortic aneurysm However, statin use is risky. Some people have elevated liver aminotransferases and fatigue, and some people have serious adverse reactions rhabdomyolysis and have walked through the ghost gate. Are the serious side effects of statin use due to improper use of the drug? What details should I pay attention to when taking statins?
▍A serious adverse drug reaction event, 82-year-old Uncle Liu, almost had a big problem because of the side effects of the statin. 15 years ago, he was brought to the emergency department with an acute myocardial infarction, and the doctor fitted him with a stent. After that, I took the secondary prevention drug for coronary heart disease according to the doctor's instructions. Four years ago, he went to the emergency department again because of acute inferior myocardial infarction and had a second stent installed. After surgery, a variety of medications were taken daily, including aluminum-magnesium pills, atorvastatin calcium tablets, metoprolol succinate, and enalapril maleate tablets. However, on November 29, 2021, the cardiac enzyme spectrum and liver and kidney function tests showed that Uncle Liu had heart failure, so the doctor decided to replace enalapril tablets with sacubitril-valsartan tablets. At the end of December, Uncle Liu suddenly felt that his limbs were sore and weak, and his urine was like tea, thinking that it was just a cold and he didn't take it to heart. On January 3, 2022, due to worsening chest tightness and shortness of breath, Uncle Liu was rushed to the hospital. The examination showed that the cardiac enzyme spectrum and liver and kidney function indicators were obviously abnormal, the urine routine showed positive occult blood and pathological casts, and the urine routine showed occult blood (++), indicating that the urine hemoglobin or myoglobin exceeded the standard. Creatine kinase (CK) is more than 86 times higher than the upper limit of normal, which means that there may be serious muscle damage or heart problems in the body, such as rhabdomyolysis or myocardial infarction. A markedly elevated serum creatinine (Cr) indicates impaired renal function and signs of acute renal failure or chronic kidney disease. The pharmacist believes that it may be the interaction between atorvastatin and sacubitril valsartan tablets, which causes the adverse reaction rhabdomyolysis. Doctors are advised to suspend atorvastatin and give treatment with insulin and glucose. After stopping the drug for 3 days, Mr. Liu's cardiac enzyme profile improved. Five days after stopping the drug, further test results showed that the indicators continued to improve, and the soreness of the limbs was also significantly alleviated. It seems that the withdrawal and treatment have had an effect.
▍Is rhabdomyolysis syndrome a "dissolution" of muscles? Rhabdomyolysis syndrome (RM) is a severe muscle injury in which muscle-associated enzymes such as creatine kinase (CK) are markedly elevated, possibly more than 5 times the upper limit of normal or more than 1000 IU/L in absolute terms. In rhabdomyolysis syndrome, the word "dissolution" does not mean the dissolution of muscle, but the rupture of muscle cells and the leakage of internal substances. Let's put it this way, our muscle cells are like small houses filled with all kinds of substances. When these cells are damaged or stressed, their "walls" break like they have collapsed. As a result, substances inside the cells, such as myoglobin and other enzymes, leak into the bloodstream. When these substances enter the bloodstream, they can cause damage to other parts of the body, especially the kidneys. The kidneys are a bit like the body's filters, and if too much of these substances are leaked, it can lead to kidney failure. Symptoms are mainly muscle pain, muscle weakness, strong brown urine, and can also be manifested as fever, fatigue, tachycardia, nausea, vomiting and abdominal pain. People who are susceptible to rhabdomyolysis1. The elderly, especially the thin, frail elderly women and elderly patients over 65 years old, should not take statins at a dose of more than 3/4 of the normal dose for adults. 2. Older adults with multiple chronic diseases at the same time3. People with underactive thyroidism4. People with a history or family history of drug-induced myopathy5. People with poor kidney function6.Diabetic7. People who are treated with multiple medications may interact with each other, increasing the risk. 8. Patients who have undergone major surgery are taking statins and are at increased risk if major surgery is to be performed. 9. Consumption of grapefruit juice can affect statin metabolism and increase the risk of side effects. 10. Long-term heavy alcohol consumption also increases the risk
People with the above high risk should monitor creatine kinase levels and liver function 1-3 months after taking the drug, 6 months, 12 months, 18 months after taking the drug, and every year thereafter, so as to detect and treat adverse reactions early.
Once it is found that the creatine kinase level reaches 3 ~ 10 times of the upper limit of normal, the dose should be reduced or stopped, and the drug should be rechecked within 1 week. If creatine kinase is more than 10 times, in addition to stopping the drug, it is necessary to check the renal function and urine routine immediately, and recheck it after 4 weeks, and the doctor will determine whether to continue the drug according to the situation.
▍ Take statins all year round, several problems to pay attention to
1. Comply with the indications and contraindications, do not overdose statins indiscriminately, and are not suitable for everyone. The dos and can'ts are as follows: Indications for high cholesterolemia, coronary heart disease, or stroke are at high risk, and your doctor may recommend taking a statin. Contraindications: Severe liver disease, kidney disease, pregnancy or lactation, allergy to statins, etc., statins are not recommended.
Adverse reactions of statins mainly include abnormal liver function, muscle complications (including myalgia, myositis, myopathy, and rhabdomyolysis), new-onset diabetes, headache, insomnia, depression, and gastrointestinal symptoms such as dyspepsia, diarrhea, abdominal pain, and nausea. Among them, rhabdomyolysis is one of the most serious side effects of statins.
The higher the dose of a statin, the more likely it is to have side effects. Asians who use high-dose statins have a higher risk of muscle side effects than people in Europe and the United States. Therefore, most experts are clearly opposed to the use of high-dose statins.
2. Be careful when using drugs and food
Statins are metabolized primarily through the liver's "scavenger" cytochrome P450 system, and some of these statins rely specifically on the "specialized channel" of CYP3A4. Therefore, statins should be used with caution when combining with drugs that affect the CYP450 enzyme.
1) When lovastatin, simvastatin and atorvastatin are mainly metabolized by the liver enzyme CYP3A4, and CYP3A4 inhibitors (including macrolide antibiotics such as erythromycin, cimetidine, verapamil, protease inhibitors, pyrrole antifungals such as ketoconazole, and anti-rejection drug cyclosporine, etc.), the consequence is that the metabolism of statins is inhibited (cannot be excreted), which doubles the concentration of statins in the blood, resulting in an increased risk of myostoxicity.
2) The anti-tuberculosis drug rifampicin is an inducer of CYP2C9 and reduces the bioavailability of fluvastatin by 50%. When used in combination with statins, care should be taken to adjust the dose of the drug.
3) When statins are combined with other hypolipidemic drugs (niacin, gemfibrozil, fenofibrate or fibrate), the incidence of rhabdomyolysis and acute renal failure increases, and the combination should not be used.
4) The combination of statins and oral anticoagulants (warfarin) will increase the effect of anticoagulants, and the dose of anticoagulants should be adjusted in time.
5) Combined with antihypertensive drugs or diuretics of CYP3A4 inhibitors such as verapamil, diltiazem, mibelaxidil, etc., the risk of muscle-damaging diseases increases by 1-8 times.
6) When taking statins, do not drink grapefruit juiceGrapefruit juice (grapefruit juice) contains ingredients that inhibit CYP3A4 and can increase the blood concentration of drugs metabolized by CYP3A4.
4. Start with a small dose, and start with a small dose of statins. After a period of observation, if there are no adverse effects, the dose can be increased in an appropriate amount as needed. This minimizes the risk and results in the best possible outcome.
5.. Monitor liver function regularly and observe adverse reactions closely
When taking statins, pay attention to monitoring liver function and treat it according to the situation to ensure the safety of medication.
When taking drugs in combination, pay attention to closely observe and monitor creatine kinase and liver and kidney function, and deal with adverse reactions in time once they are found.
Ways to reduce statin side effects
The combination of statins and ezetimibe can reduce the dose of statins, thereby reducing side effects. The addition of ezetimibe reduces the amount of statin used, but the efficacy is the same, reducing the risk of myopathy and rhabdomyolysis.
Bibliography:
1.成人动脉粥样硬化性心血管疾病一级预防的风险评估策略，Peter WF Wilson, MD，Professor of Medicine，Emory University School of Medicine，uptodate
2. Zhao Fukun, Li Jie, Luo Min, et al. Atorvastatin combined with sacubitril-valsartan induced rhabdomyolysis in 1 case [J]. Chinese Journal of Hospital Pharmacy, 2022, 42 (22): 2436-2438. DOI:10.13286/j.1001-5213.2022.22.23.
3. Wen Donghua. Adverse reactions of statins and their prevention and treatment [J]. Herald of Medicine, 2013, 32 (06): 818-820.
4. Ding Hongmei Geng Deqin, rhabdomyolysis - maybe it has something to do with the statins you take! 2023-09-09 Divine Manor
5. Metabolic Interactions of Cardiovascular Drugs Commonly Used in Clinical Practice, Jiangsu Provincial Hospital of Traditional Chinese Medicine, 2015-11-20
6. How much do you know about statins (II)——Statin-related rhabdomyolysis, Department of Endocrinology, Shanghai Punan Hospital 2022-01-06
7. Take you to know statins, Henan Provincial Hospital of Traditional Chinese Medicine, 2019-08-03
8. Drug-induced rhabdomyolysis, Liying Lu, Laboratory Medicine, 2022-04-24
9. Guidelines for the management of blood lipids in China (Grassroots Edition, 2024)
Tips: This article does not represent professional diagnosis and treatment opinions, and specific diagnosis and treatment should be carried out under the guidance of professional doctors.
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