Understanding Lipid-Lowering Drugs Scientifically: From Classification and Drug Selection to In-Depth Analysis of the Multiple Prevention and Treatment Values ​​of Statins

Lipid-lowering Drug Application

What are some commonly used lipid-lowering drugs?

How many categories can lipid-lowering drugs be divided into according to their effects? They can be divided into two main categories according to their effects.

① Drugs that primarily lower cholesterol:
a. Statins: Commonly used ones include lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin.
b. Bile acid sequestrants: Commonly used ones include cholestyramine and colestipol.

② Drugs that primarily lower triglycerides:
a. Fibrates: Commonly used ones include fenofibrate, gemfibrozil, and bezafibrate.
b. Niacin: Commonly used ones include niacin and acipimox.

How to rationally select lipid-lowering drugs? Lipid-lowering treatment should be based on non-drug therapy, and drugs should be selected under the guidance of a doctor according to individual circumstances.

① High cholesterol and blood pressure: If triglycerides and high-density lipoprotein cholesterol are normal, statins are the first choice.

② Hypertriglyceridemia: Fibrates are the first-line treatment.

③ Low HDL cholesterol: For isolated HDL cholesterol deficiency, non-pharmacological treatment should be the foundation, and fibrates, niacin, or bile acid sequestrants can be used, with niacin being the most effective.

④ Mixed dyslipidemia: Total cholesterol, triglycerides, and LDL cholesterol are all elevated. a. If triglycerides are elevated but <3.4–4.5 mmol/L, while total cholesterol or LDL cholesterol is very high, statins are the first-line treatment. b. If triglycerides are significantly elevated but >5.65 mmol/L, and total cholesterol or LDL cholesterol is mildly to moderately elevated, fibrates should be the first-line treatment. Statins

What are statins? How do they work? Statins are the most commonly used lipid-lowering drugs. Statins are HMG-CoA reductase inhibitors, and their English names all end in "tatin," such as lovastatin. Statins inhibit HMG-CoA reductase activity, reducing cholesterol synthesis in the liver, stimulating the production of low-density lipoprotein (LDL) receptors, and enhancing LDL clearance from plasma. Currently, it is believed that in addition to their direct lipid-lowering effects, statins also have antioxidant, anti-inflammatory, cell proliferation-inhibiting, immunosuppressive, endothelial and vasomotor functions, and platelet aggregation and thrombus formation effects.

What are the characteristics of statins? The characteristics of statins are as follows.

① Statins can significantly reduce total cholesterol in the blood by 22%–40%, especially significantly reducing LDL cholesterol by 18%–55%, while also reducing triglycerides by 7%–35% and increasing HDL cholesterol by 5%–15%. Therefore, statins can be considered to have a comprehensive effect on regulating dyslipidemia, primarily by lowering total cholesterol.

② Statins can delay or prevent the development of atherosclerotic plaques in the coronary arteries, and even cause plaques to shrink or disappear, especially in severe cases.

③ Regardless of whether individuals have risk factors for coronary heart disease or are already diagnosed with coronary heart disease, and regardless of the extent of their elevated total cholesterol levels, statins can significantly reduce the incidence of coronary heart disease (such as angina pectoris and myocardial infarction), mortality, and disability rates (such as heart failure and severe arrhythmias) associated with coronary heart disease, while also significantly reducing the risk of stroke. In recent years, researchers have compared statins with several other classes of lipid-lowering drugs. Results show that statins are currently the only drugs that can significantly reduce blood cholesterol (an average decrease of 22.9%) and the mortality and disability rates from coronary heart disease (reduced by about one-third).

④ Recent studies have found that patients who take statins immediately after an acute myocardial infarction have a significantly lower incidence of unexpected events (angina, recurrent myocardial infarction, heart failure, sudden death, etc.) within 30 days of the infarction compared to those who do not take statins.

⑤ Currently marketed statins are safe and effective and can be taken long-term. For example, more than 60 million patients worldwide are taking atorvastatin.

What other effects and uses do statins have besides lipid regulation? The remarkable efficacy of statins comes not only from adjusting blood lipids but also from many other effects.

① Improves vascular endothelial function and promotes vasodilation related to vascular endothelial function.

② Antioxidant effect: Reduces the formation of oxidized low-density lipoprotein, thereby helping to reduce lipid intrusion into the vascular endothelium of atherosclerotic plaques and inhibiting plaque development.

③ Anti-inflammatory effect: Studies have shown that the occurrence and development of atherosclerotic plaques is actually an inflammatory process, especially in the process of plaque instability, rupture, thrombus formation, and ultimately leading to angina pectoris, acute myocardial infarction, or even sudden death. Inflammation plays a crucial role in this process. Recently, the anti-inflammatory effects of statins have also attracted the attention of physicians in other disciplines (such as rheumatology).

④ Inhibits or disrupts certain enzymes that affect the stability of atherosclerotic plaques, thereby helping to stabilize atherosclerotic plaques and reduce the occurrence of acute coronary events.

⑤ Inhibits the proliferation of fibrous tissue within the plaque, delaying plaque development.

⑥ Anticoagulant and antithrombotic effects.

Based on the above, statins have the following uses.

① Prevention and treatment of cardiovascular and cerebrovascular diseases: Multiple large-scale clinical trials have shown that statins, as primary and secondary preventative medications for coronary heart disease, can reduce the incidence of coronary heart disease by 25%–60% and the risk of death by 30%. They can also significantly reduce the risk of angina pectoris and cerebrovascular accidents, and decrease the probability of interventional coronary artery bypass grafting and coronary angiography. Currently, statins are considered the only drugs that can reduce the overall mortality rate of patients with coronary heart disease. When used for aneurysms, statins can also directly act on the aneurysm wall cells, increasing the aneurysm wall's strength and making it less prone to rupture. Previously, it was believed that once arteriosclerosis formed, it was incurable and could only gradually worsen. Recent research shows that intensive lipid regulation may reverse atherosclerosis, which shakes the traditional view that atherosclerosis is incurable.

② Kidney protection: Statins can reduce kidney damage by decreasing abnormal lipid metabolism, and can also directly act on the kidneys, reducing kidney damage, alleviating glomerular sclerosis, and delaying renal failure, especially showing good efficacy in diabetic nephropathy.

③ Treatment of osteoporosis: Statins can promote bone formation, increase bone density, repair bone microstructure, strengthen bones, and reduce the risk of fractures. Studies have found that statins can reduce the incidence of fractures by 45%; even short-term use has a protective effect on bones.

④ Treatment of biliary cirrhosis: Recent studies suggest that statins have anti-fibrotic effects and can be used to treat biliary cirrhosis.

⑤ Prevention and treatment of Alzheimer's disease: Some lipid-lowering studies have found that elderly people with high cholesterol who use statins have a 70% lower chance of developing Alzheimer's disease than those who do not.

What drugs or foods can cause adverse reactions with statins? Most statins are metabolized by hepatic cytochrome P450 (CY P450). Therefore, adverse reactions can occur when used in combination with other drugs or foods related to the cytochrome P450 drug metabolism system. For example, the combined use of statins and fibrates increases the risk of myopathy. For example, gemfibrozil increases statin concentrations by inhibiting cytochrome oxidase (P450-3A4) and may also inhibit statin glucuronidation, leading to adverse reactions. Drugs that can interfere with statin metabolism include:

① Enzyme inducers: phenytoin, barbiturates, reserpine, troglitazone, carbamazepine. Concomitant use of statins with these drugs can decrease the blood concentrations of the aforementioned drugs, reducing their effectiveness.

② Enzyme inhibitors: ketoconazole, fluconazole, itraconazole, macrolides, tricyclic anti-inhibitors, cyclosporine, thiamethoxam, verapamil, amiodarone, corticosteroids, protease inhibitors. Concomitant use of these drugs with statins can increase the blood concentration of statins, potentially causing myopathy. Statins should also not be taken with the following foods: grapefruit, pomelo, bergamot, and spirits. If the above-mentioned foods are used together with statins, the blood concentration of statins may increase under the influence of liver enzymes, thereby causing myopathy or increasing transaminase levels.