1.Trihydroxytrimethylol its glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
These drugs are inhibitors of intracellular cholesterol synthesis rate-limiting enzyme, namely HMG-CoA reductase. They are the most widely used class of lipid regulators in clinical practice, and are often called statins because their English names contain “statin”. Since the first statin was approved for the treatment of hyperlipidemia in 1987, there are now five major statins available for clinical use.
The mechanism of the hypolipidemic effect of statins is currently believed to be due to the inhibition of the rate-limiting enzyme, HMG-CoA reductase, in the early stages of intracellular cholesterol synthesis, resulting in a decrease in intracellular free cholesterol and an increase in the number and activity of intracellular LDL receptors through feedback upregulation of LDL receptor expression on the cell surface, thereby accelerating the clearance of VLDL residues (or IDL) and LDL from circulating blood. clearance.
(1) Lovastatin
The main ingredients of the product are also lovastatin. The common dose is 10~-80mg/d nightly. For patients with type II hyperlipoproteinemia, lovastatin 20mg/d lowered TC, LDL-C and TG by 17%, 24% and 10% respectively, and increased HDL-C by 7.2%; lovastatin 80mg/d lowered TC, LDL-C and TG by 29%, 40% and 19% respectively, and increased HDL-C by 9.5%.
The side effects of this drug are rare, with occasional abdominal pain, diarrhea, constipation, muscle cramps, fatigue, skin rash and blurred vision. There may be abnormal liver function and elevated CK. Occasionally, clinical manifestations of myopathy with significant CK elevation (more than 10 times the upper limit of normal value) may occur.
(2) Simvastatin
The trade name of Simvastatin is Sulforaphane, Risuida, Kybixin, Zeligho, Sulforaphane, and Simcoe. 5~40mg/d, taken every night. Since its introduction in 1988, simvastatin has been used in clinical practice for more than 10 years, and many studies and clinical observations have confirmed that the drug has a good safety profile for long-term use. Long-term experimental studies of simvastatin applied different doses (2.5-10 mg/d, 20-30 mg/d, 40 mg/d, and >40 mg/d in 16%, 23%, and 57%, 4%, respectively).
The effect of long-term treatment (>1 year, 2 years, 3 years 4 years in 36%, 26%, 23%, and 15%, respectively, with a mean of 1.5 years). Simvastatin treatment has been shown to reduce TC by a mean of 28-30%; LDH-C by a mean of 36-39%; TG by a mean of 11-16%; and HDL-C by a mean of 10-14%. Side effects of simvastatin are rare and include constipation, abdominal pain, dyspepsia, abdominal distention and nausea. Simvastatin-induced liver damage is uncommon and manifests mainly as mild elevations in serum transaminases.
A transient increase in creatine kinase (CK) (greater than 3 times the normal standing value) can occur in about 5 of patients treated with simvastatin and is usually not clinically significant. Myositis, with or without elevated serum CK levels, can occur in a very small number of people taking HMG-CoA reductase inhibitors, but this myositis is self-limiting.
(3) Pravastatin
Trade name Pravastatin, Meperidine, 10-40 mg/d, nightly dose. A multinational study of pravastatin looking at the lipid-lowering effect in 1026 patients with hypercholesterolemia showed that 13 weeks of treatment with pravastatin (20 mg/d) reduced TC, LDL-C and TG by 19%, 26% and 12%, respectively. Three large-scale clinical studies confirmed that pravastatin 40 mg/d reduced TC, LDL-C and TG by 18-20%, 25-28% and 11-14%, respectively, and increased HDL-C by 5%.
The main adverse effects are mainly manifested as elevated liver transaminases and are related to the drug dose, but no long-lasting liver damage due to this drug has been reported so far. Transaminases need to be measured in those taking pravastatin and should be used with caution when transaminases exceed three times the upper limit of normal. Rarely, rhabdomyolysis and immune myopathy have been reported.
(4) Fluvastatin
The trade name is Sikor, 10 to 40 mg/d, taken nightly in a single dose. In patients with primary hypercholesterolemia, daily administration of 20-80 mg of fluvastatin can reduce TC, LDL-C and TG by 15-21%, 19-31% and 1-12%, respectively, and increase HDL-C by 2-10%. It can continue to reduce LDL-C by more than 6%. Although serious side effects of fluvastatin are rarely reported, there are still reports of muscle pain (myositis) caused by fluvastatin. 0.3% of patients taking fluvastatin develop asymptomatic creatine kinase elevation (10 times higher than the upper limit of normal), which should be rapidly discontinued.
(5) Atorvastatin
Trade name Lipitor, Arle, 2.5 mg to 20 mg/d, nightly dose. The usual dose (10-80 mg/d) of atorvastatin can lower LDL-C by 40-60%, lower TG by 23-45%, and raise HDL-C by 5-9%, with parallel changes in ApoB and LDL-C. In primary hypertriglyceridemia, significant efficacy was also obtained with atorvastatin alone. The drug is well tolerated, and the occurrence of adverse effects does not correlate significantly with the atorvastatin dose.
Persistent transaminase elevations of more than three times normal have occurred in a small number of patients, mostly within 16 weeks of treatment. Rarely, myopathy has been reported with this drug.
(6) Rosuvastatin calcium: 10-20 mg/d in the evening, taken nightly. All formulations require nightly dosing, except atorvastatin and resulvastatin, which can be taken at any time.
(7) Comparison of lipid-lowering efficacy of various statins
Currently, there are five types of statin lipid-lowering agents available for clinical use in China, and their respective lipid-lowering effects and effects on the prevention and treatment of coronary heart disease may be different, but within a certain dose range, the efficacy of these five statins in reducing total cholesterol, LDL-C and triglycerides and increasing HDL-C is comparable (Table 1). It was also found that the effects of statin-lowering drugs on lowering total cholesterol and LDL-C, although correlated with drug dose, were not linear.
When the dose of statin-lowering drugs was doubled, the magnitude of lowering total cholesterol increased by only 5%, and the magnitude of lowering LDL-C increased by 7%.
2.Beetle
Betaine can enhance the activity of lipoprotein lipase, accelerate VLDL catabolism, and inhibit the synthesis and secretion of VLDL in the liver. These drugs can reduce TG22-43%, and reduce TC only 6-15%, and have different degrees of elevated HDL-C scale effect, its indications for hypertriglyceridemia or mixed hyperlipidemia with mainly elevated triglycerides.
(1)Fenofibrate
The half-life of fenofibrate is up to 20 hours, but the absorption rate after meals is only 60%. Micronized fenofibrate preparation (also known as Lipin, usage 0.2 g 1 time/d) can make TG decrease 39~55%, TC decrease about 20%, LDL-C decrease 22~27%, small and dense LDL-C (sLDL-C) decrease 21.5%, VLDL-C decrease 54~63%, HDL-C increase 26~29%, ApoB decrease 22~23 and decreased Lp(a) and increased Apo AI.
In a few patients, mild abdominal distension occurs one week after the use of particulate fenofibrate, and disappears within 4 weeks without special discomfort. Micronized fenofibrate can cause mild elevation of glutamic oxalacetic transaminase and glutamic alanine transaminase.
(2) Gemfibrozil
Gefirozil reduces TG by 43% and also reduces the incidence of coronary heart disease events. However, because of its weak effect on lowering total cholesterol, gefirozil reduced TG by 31% and increased HDL-C by 6% after 1200 mg/d treatment, with no significant change in LDL-C; the adverse effects were similar to those of fenofibrate.
(3) Benzafibrate
The trade name of benzofibrate is Abeta or Bifid, 0.2g 3 times/d. The trade name of extended-release long-acting formulation is Lipocompound. After treatment with benzofibrate extended-release formulation (400 mg/d), TG decreased by 21%, TC decreased by 4%, LDL-C decreased by 6%, and HDL-C increased by 18%. Adverse effects were comparable to those of fenofibrate.
3.Dosage precautions
For specific patients, appropriate lipid-lowering drugs should be selected according to their plasma abnormalities and their coronary heart disease risk. There is no recognized standard of suitable lipid-lowering drugs. From the perspective of coronary heart disease prevention and treatment, it is generally believed that suitable lipid-lowering drugs should have the following characteristics.
(1) The lipid-lowering effect, especially the cholesterol-lowering effect, is precise; the application of conventional doses can reduce TC by 20% (LDL-C by 25%) or more within 4-6 weeks, and has the effect of reducing TG and increasing HDL-C;
(2) It is well tolerated by patients, with few adverse effects and no serious toxicities or side effects;
(3) It has been shown to significantly reduce cardiovascular mortality and disability, and does not increase non-cardiovascular mortality;
(4) has a good cost-benefit ratio. The large body of clinical evidence available suggests that statin lipid-lowering agents should be preferred for the prevention and treatment of coronary artery disease.
Treatment of dyslipidemia generally requires long-term adherence to achieve significant clinical benefit. Plasma cholesterol, triglycerides and HDL-C should be rechecked within 4-6 weeks after initiation of drug therapy, and medications should be adjusted according to changes in lipids. If lipids are not reduced to the standard, the dose of medication should be increased or other lipid-lowering drugs should be changed, and combination medication should be considered.
If the lipids have been reduced to normal or have reached the target value after treatment, continue to use the same dose of medication unless the lipids have been reduced to a very low level, and generally do not reduce the dose of medication. In case of long-term continuous medication, blood lipids should be rechecked every 3-6 months, and liver and kidney function and creatine kinase should be rechecked at the same time.