Blood lipids are the general term for cholesterol in plasma (also divided into high-density lipoprotein cholesterol and low-density lipoprotein cholesterol), triglycerides and esters such as phospholipids. The main components of blood lipids that are closely related to clinical and disease are cholesterol and triglycerides. If triglycerides and (or) total cholesterol increase, it is dyslipidemia, also known as hyperlipidemia. Dyslipidemia is the main cause of atherosclerosis, and atherosclerosis is the basis of cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, cerebral infarction and cerebral hemorrhage, which brings great harm to people’s health. .
Dyslipidemia can be divided into four types: hypercholesterolemia, hypertriglyceridemia, low-high-density lipoprotein cholesterolemia, and mixed hyperlipidemia. At present, the treatment of dyslipidemia is divided into non-drug and drug treatment: non-drug treatment measures include diet and other lifestyle adjustments to prevent hyperlipidemia, which is also the basis for the treatment of dyslipidemia; in correcting secondary causes or removing predisposing factors After 3 to 6 months of lifestyle interventions such as weight control, reasonable diet, alcohol restriction, aerobic exercise, and smoking cessation, patients who still cannot improve need to start medication in time.
Lipid-lowering drugs are divided into 5 categories, each of which has different targets
At present, the commonly used lipid-lowering drugs in clinical There are many, can be divided into the following five categories:
such as simvastatin, pravastatin, atorvastatin, rosuvastatin and so on. In addition, the Chinese patent medicine Xuezhikang also contains statins. Statins mainly reduce low-density lipoprotein cholesterol (LDL-C, also called “bad cholesterol”) and total cholesterol (TC), and also have a certain auxiliary effect on lowering triglycerides (TG). The main adverse reactions are abnormal liver function and myositis.
Elevated levels of low-density lipoprotein cholesterol (LDL-C) are recognized as an independent risk factor for cardiovascular events. Statins are currently recognized as a cardiologist because they can effectively reduce LDL-C and reduce the incidence of cardiovascular events. Lipid-lowering drugs with the strongest vascular protection and the most widely used are mainly used for primary and secondary prevention of cardiovascular diseases, and have become the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD).
such as fenofibrate, bezafibrate, gemfibrozil and the like. These drugs mainly reduce triglycerides (TG), and can also increase high-density lipoprotein cholesterol (HDL-C, also known as “good cholesterol”) levels, and slightly lower cholesterol (TC) and low-density lipoproteins Cholesterol (LDL-C), its adverse reactions are similar to those of statins. Clinically, it is mainly used for hypertriglyceridemia, mixed hyperlipidemia with elevated triglycerides, etc.
3. nicotinic acid
as acipimox like. This kind of drugs mainly lowers triglycerides (TG) and raises high-density lipoprotein cholesterol (HDL-C). In addition, it can also reduce low-density lipoprotein cholesterol (LDL-C) and cholesterol (TC). Among all lipid-lowering drugs, niacins increase HDL-C the strongest. The main adverse reactions include facial flushing, gastrointestinal discomfort, liver damage, elevated uric acid, and elevated blood sugar. Therefore, patients with chronic liver disease and gout are contraindicated.
4. Cholic acid chelating agents (resin)
such as cholestyramine (cholestyramine) can combine with bile acid in the intestine to inhibit the absorption of intestinal cholesterol (TC), and the main effect is to lower blood cholesterol. This type of drug is more irritating to the gastrointestinal tract and often causes constipation, so it is rarely used clinically.
The cholesterol absorption inhibitors
such as ezetimibe, the drug by inhibiting the absorption of cholesterol in the small intestine to function to reduce low density lipoprotein cholesterol (LDL-C) based, but weaker than lipid-lowering statins, It is suitable for patients who cannot tolerate statins or whose blood lipids cannot reach the standard when using statins alone. The drug can be used alone or in combination with statins. Because of its safety and good tolerance, it is more suitable for elderly patients.
Hypertriglyceridemia, it is more suitable to choose fibrate lipid-lowering drugs
Statins are currently the most widely used lipid-lowering drugs, but as mentioned above, there are 4 types of dyslipidemia. If the patient has hypertriglyceridemia-based dyslipidemia, fibrate drugs are more appropriate . Such drugs can reduce low-density lipoprotein cholesterol (LDL-C) by 20%, high-density lipoprotein cholesterol (HDL-C) by 5%-20%, and triglycerides (TG) by 25%-50%.
Taking fenofibrate as an example, its common dosage forms are: (1) Fenofibrate tablets/capsules, orally, 0.1 g each time, 3 times a day. After fenofibrate is micronized, the specific surface area increases, which speeds up the dissolution rate of the drug and increases the absorption of the drug. (2) Fenofibrate capsules (II), orally, 0.2 grams once, once a day. The preparations prepared by combining the micronization technology and the micro-powder coating technology have faster drug dissolution and more drug absorption. (3) Fenofibrate tablets (Ⅲ), orally, 0.16 g each time, once a day, swallow whole tablets. It should be noted that because food can increase the absorption of fenofibrate and reduce gastrointestinal reactions caused by fenofibrate, all fenofibrate preparations must be taken with meals.
In addition to lipid-lowering effects, fenofibrate has the following characteristics: ①It has a protective effect on microangiopathy in patients with type 2 diabetes, can delay the progression of retinopathy in patients with type 2 diabetes, reduce the need for laser treatment, and slow down the progression of microalbuminuria, and It can reduce the risk of microvascular amputation in patients with type 2 diabetes. ②It can inhibit the reabsorption of uric acid in the proximal tubules of the kidney, promote the excretion of uric acid in the kidney, and reduce the uric acid in plasma by an average of 25%. It is recommended for patients with hyperuricemia and gout with hypertriglyceridemia, and fenofibrate is the first choice for lipid-lowering drugs.
Fenofibrate is a first-line drug for lowering triglycerides (TG). If the following conditions exist, fenofibrate treatment should be started: (1) When TG ≥ 5.6mol/L, fenofibrate treatment should be started immediately to prevent acute Pancreatitis; (2) Primary prevention for high-risk cardiovascular disease patients (such as diabetic patients) whose LDL-C has reached the standard but TG is still ≥2.3mmoL/L; (3) LDL-C has reached the standard, but TG is still ≥2.3mmoL /L secondary prevention of ASCVD patients.
However, in the prevention of atherosclerotic cardiovascular disease (ASCVD), when the triglyceride (TG) level is less than 5.6mmol/L, statins should be the mainstay. This is because statins can lower both low-density lipoprotein cholesterol (LDL-C) and triglycerides, but they are relatively weak.
Combined with statins for lipid regulation, fenofibrate is the first choice
It should be noted that, in order to improve the efficacy of lipid-lowering and reduce the incidence of adverse reactions, the combined application of different types of lipid-lowering drugs is a better choice for improving the efficacy of lipid-lowering. Combination medication can give full play to the complementary and synergistic effects of drugs, which is beneficial to comprehensively adjust dyslipidemia, reduce drug dosages, and increase lipid-lowering efficacy. Since statins have a positive effect and few adverse reactions at conventional doses, statin-based combination drugs have become the first choice for combined lipid-lowering therapy under the premise of safety and effectiveness.
In combination therapy with statins, fenofibrate is the first choice. Gemfibrozil is also one of the fibrate drugs, but it can inhibit CYP2C8, CYP2C9, CYP2C19, CYP1A2 and other liver drug enzymes. It can also inhibit UDP-glucuronyl transferase. When combined with statins, it will Increase the peak blood concentration of statins by 1.8 to 2.8 times, and side effects will increase accordingly. Panofibrate has no significant effect on the drug metabolism of statins.
However, fenofibrate may also cause muscle damage. When used in combination with statins, the risk of muscle damage increases. Therefore, it is necessary to closely observe whether there are signs of muscle damage such as severe muscle pain and muscle weakness. Because of concerns about the liver, kidney, and muscle toxicity of the combination of statin and fibrate, many doctors often temporarily stop statin and switch to fibrate, and then switch to statin after the triglyceride decreases. This is unreasonable. For patients with indications for statin therapy (especially coronary heart disease), discontinuing statin therapy can significantly increase the risk of adverse cardiovascular events. Therefore, unless the patient really cannot tolerate the combination of the two drugs, statins should not be discontinued. Because human body-derived cholesterol is mainly synthesized at night, and statins can block the self-synthesis of cholesterol, you can take fenofibrate in the morning and statins before going to bed to avoid the overlap of the peak blood concentration of the two types of drugs. Reduce the occurrence of adverse drug reactions.
Other drugs that are not recommended for combined use include:
1. Coumarin-based oral anticoagulants. Fenofibrate may enhance the efficacy of coumarin-based anticoagulants (such as warfarin), so when combined with coumarin-based oral anticoagulants, the dose of oral anticoagulants should be reduced, and coagulation indicators should be monitored more frequently , Adjust the dose until it reaches a stable level.
2. Immunosuppressants. For example, cyclosporine and tacrolimus are nephrotoxic, which can reduce creatinine clearance and increase serum creatinine. While fibrates are mainly excreted by the kidneys, the interaction between immunosuppressive agents and fenofibrate may cause deterioration of renal function. Therefore, the risks and benefits of the combined use of fenofibrate and immunosuppressants should be carefully weighed; if it must be used, the minimum effective dose should be used and renal function should be monitored.
3. Cholic acid chelator. The main reason is that bile acid chelating agents (such as cholestyramine) will be combined with drugs taken at the same time. Therefore, fenofibrate should be taken at least 1 hour before or 4-6 hours after taking the bile acid binding agent to avoid hindering the Norbert’s absorption.
Avoid 7 Misunderstandings in Treating Dyslipidemia
Different lipid-lowering drugs have different characteristics, lipid-lowering intensity, metabolic pathways, half-life, and side effects. Clinically, they need to be rationally selected according to different types of dyslipidemia, patients’ liver and kidney function, and control goals. Statins are the first choice for hypercholesterolemia; fibrates are the first choice for simple hypertriglyceridemia; for mixed hyperlipidemia, statins or statins and fenofibrate can be used alone, depending on the specific situation.
In addition, we must pay attention to avoid the following misunderstandings.
Misunderstanding 1: Only when blood lipids are high, lipid-lowering treatment is needed.
After people get the blood lipid test sheet, they often first check whether the test result is within the normal reference value range. As long as it does not exceed the range, the blood lipids are considered normal and no treatment is required. As everyone knows, the normal range of blood lipids varies from person to person, and different groups of people have different standards. The normal range shown on the laboratory test sheet is mainly applicable to healthy people. In other words, the blood lipid target value is stratified by risk, and the higher the risk factor, the stricter the requirement. Taking low-density lipoprotein cholesterol as an example, different groups of people have different target values: healthy people <3.4mmol/L; hypertension or diabetes <2.6 mmol/L or less; hypertension and diabetes, acute coronary syndrome, stroke, peripheral Atherosclerosis <1.8mmol/L. Most hospitals’ blood lipid test sheets do not give different reference values for different groups of people. Therefore, even if the blood lipid test sheet shows normal, blood lipids may not necessarily be normal. Doctors should assist in judging and guiding treatment strategies. Misunderstanding 2: Too much worry about the side effects of lipid-lowering drugs. Any medicine (including Chinese medicine) has certain side effects, and lipid-lowering medicines are no exception. Both statins and fibrates can cause abnormal liver function (increased transaminase), muscle damage (often manifested as muscle pain, increased muscle enzymes, and rhabdomyolysis is extremely rare), but the incidence is not high, and most of them can be after stopping the drug Back to normal. The benefits of using lipid-lowering drugs far outweigh the side effects, and patients do not need to stop eating due to choking. As long as you pay attention to observation and monitoring (liver function, muscle enzymes, etc.) during the medication process (especially in the early stage of medication), safety is completely guaranteed. Generally speaking, when transaminase rises by more than 3 times and creatine kinase rises by more than 5 times, the drug should be stopped in time. Some patients who are worried about the side effects of these drugs, refuse to use drugs or dare not take drugs for a long time, etc., do not follow the doctor's advice. Misunderstanding 3: Relying completely on controlled diet or completely relying on drugs. Neither extreme approach is desirable. On the one hand, low-fat diets tend to lower triglycerides (TG) better, but lower-density lipoprotein cholesterol (LDL-C) is less effective. This is because the level of triglyceride (TG) has a lot to do with diet, while LDL-C is mainly endogenous and is mainly synthesized by the liver. On the other hand, if you are completely dependent on drugs and do not carry out lifestyle interventions, it will be difficult to control blood lipids to reach the standard, and the side effects of the drugs may increase due to the excessive use of lipid-lowering drugs. Therefore, to correct dyslipidemia, a two-pronged approach should be adopted, with equal emphasis on lifestyle intervention and drug treatment. Pay attention to recheck blood lipids. If blood lipids are not up to standard, and there is no adverse drug reaction, monitor once every 3 months; if blood lipids are up to standard and there is no adverse drug reaction, recheck once every 6 to 12 months. Misunderstanding 4: After the blood lipid drops, the drug can be stopped. Lipid metabolism disorder is an important risk factor leading to cardiovascular and cerebrovascular diseases. In addition to regulating blood lipids, lipid-lowering drugs (especially statins) also have many benefits such as anti-inflammatory, protecting vascular endothelium, stabilizing or even reversing atherosclerotic plaque, and reducing cardiovascular events. The longer the medication is taken, the more obvious this aspect will be. Once the drug is stopped, high blood lipids will often come back. Therefore, it is best to stick to long-term use, especially for patients with cardiovascular and cerebrovascular diseases, diabetes, and high blood pressure. If the patient does not have arteriosclerosis and related diseases (such as coronary heart disease, etc.), but simply hyperlipidemia, after statin treatment, blood lipids have reached the standard, you can try to stop the drug under the guidance of a doctor, provided that the patient can adjust lifestyle (control Diet, quit smoking and alcohol, increase exercise, etc.) to maintain normal blood lipids. Misunderstanding 5: No matter when the lipid-lowering medicine is taken, the effect is the same. Since the synthesis of cholesterol in the body is mainly carried out at night, lipid-lowering drugs (especially short-acting drugs) are best taken at night before going to bed, so that the lipid-lowering effect can be fully exerted. But for long-acting statin drugs (such as atorvastatin, rosuvastatin), the time of taking the medication can be relatively flexible, and it can be taken at a fixed time at any time of the day. Misunderstanding 6: Lipid-lowering treatment, regardless of "primary and secondary". What we call blood lipids mainly includes 4 indicators: cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Among them, HDL-C has a protective effect on the cardiovascular system, which we call "good cholesterol". Among the remaining three items, low-density lipoprotein cholesterol (LDL-C) is the most harmful, so LDL-C is usually used as the target of lipid-lowering therapy in clinical practice. To reduce LDL-C, statins should be the first choice. However, if the patient's triglyceride (TC) is abnormally elevated (>5.6mmol/L), acute pancreatitis may be induced. In this case, for safety reasons, fenofibrate should be preferred to deal with high triglycerides Esteremia, after the triglyceride drops down, add statins.
Myth 7: Fish oil can be used to lower blood fat.
Fish oil can moderately lower triglycerides, but it has no effect on lowering cholesterol, and there is no evidence to reduce the incidence of cardiovascular and cerebrovascular events. It cannot replace lipid-lowering drugs.