Lipid-lowering drugs

At the beginning of the 20th century, the first work appeared in which experimentally (on rabbits ) it was shown that the addition of cholesterol to food causes symptoms resembling atherosclerosis .

In the future, despite the very large convention of the model (cholesterol-containing foods are usually absent in normal rabbits' nutrition), a conclusion was drawn about the association of atherosclerosis disease with an increased level of consumption and accumulation of cholesterol in the body. This hypothesis was confirmed in subsequent studies with animals whose natural diet includes cholesterol (rats, monkeys).

When observing large populations of people suffering from cardiovascular diseases, it was also found that there is a certain relationship between high cholesterol and an increased likelihood of cardiovascular disease.

The use of lipid-lowering drugs gave some statistically significant effect, but for people over 70 years of age this pattern becomes less obvious.

C10AA 3-hydroxy-3- methylglutaryl-CoA reductase inhibitors (“ statins ”)

C10AA01 Simvastatin

C10AA02 Lovastatin

C10AA03 Pravastatin

C10AA04 fluvastatin

C10AA05 Atorvastatin

C10AA06 Cerivastatin

C10AA07 Rosuvastatin

C10AA08 Pitavastatin

A group of drugs (often combined under the code name "statins") designed to reduce the concentration of "cholesterol" ( LDL , LPS , HDL ) in human blood. The world's first statin was created by the American company Merck Sharp and Dohme.

• After the triumphant start of the first statins, data were obtained on some important side effects and contraindications. The main side effects are an asymptomatic increase in transaminases ^[1] , myopathy, abdominal pain, constipation ^[2] . The first generation of statins ( lovastatin , simvastatin , pravastatin ) was replaced by the second ( fluvastatin ), the third ( atorvastatin , cerivastatin ) and the fourth ( pitavastatin , rosuvastatin ), and today the approach to their use has become much more balanced. At present, the division of statins by generation is considered unreasonable, since a significant difference in their effectiveness has not been shown.

So, in the article “Statins from the perspective of evidence-based medicine” ^[3], Yu. S. Rudyk, pointing to some success in using statins, recalls “it becomes obvious that the use of statins does not completely solve the problem of preventing complications of coronary artery disease and its equivalents ...“ ... the moment when the capabilities of statins become exhausted, and further improvement of drugs, increase in their activity will not lead to a significant improvement in clinical results. Therefore, the efforts of doctors are directed to other ways of influencing the atherosclerotic process, and further progress will probably be no longer associated with statins. ” “In countries of prosperous Western Europe, 70% of patients receive statins to lower their cholesterol level, but only 53% of patients reach the target values.” (Ibid.).

• The clinical efficacy of statins is considered proven for middle-aged people.
• In addition, it is known that the level of "cholesterol" (LDL, LPS, HDL) in the blood does not always correlate with the development of atherosclerosis , and, as a consequence, with an increased risk of death from cardiovascular diseases.

A brief history of statins until 1999 is given in the source ^[4]

In addition, researchers from the University of London found that statins not only lower cholesterol, but also improve the structure and function of the heart. People taking these medications are less likely to have an enlarged heart - a sign of stress and muscle weakness. Compared with ordinary people, in patients taking medication, the left ventricle of the heart had 2.4% less muscle mass. The volumes of the left and right ventricles were also reduced. ^[five]

Medicines that are not recommended for combination with statins due to the risk of myositis and rhabdomyolysis ^[6]

• fibrates (risk of rhabdomyolysis and hepatotoxicity, possibly a combination with fluvastatin)
• nicotinic acid and its derivatives (risk of hepatotoxicity)
• macrolide antibiotics (erythromycin, clarithromycin in particular)
• cyclosporin
• azole antifungal agents
• verapamil
• amiodarone
• HIV protease inhibitors

Conditions that increase the risk of myositis and rhabdomyolysis with statins :

• mature or advanced age in combination with pathology ( diabetes and chronic renal failure )
• history of surgical interventions (statin withdrawal needed!)
• malnutrition
• liver failure
• polypharmacy
• excessive alcohol consumption
• drinking grapefruit juice

In these cases, patients should be under more careful medical supervision with enzyme control ( ALT , AST , GGTP , KFK ) at least 2 times a month. Pharmacokinetic studies have shown that patients belonging to the Mongoloid race are more sensitive to the action of statins, so lower doses should be used in such patients (<40 mg / day)

C10AB Fibrates

C10AB01 Clofibrate

C10AB02 Bessafibrate

C10AB03 Aluminum clofibrate

C10AB04 Gemfibrozil

C10AB05 Fenofibrate

C10AB06 Symphibrate

C10AB07 Ronifibrate

C10AB08 Cyprofibrate

C10AB09 Ethofibrate

C10AB10 Clofibrid

• Fibroic acid derivatives - clofibrate , bezafibrate , fenofibrate , ciprofibrate , etc. have a higher ability to lower the concentration of triglycerides and LDL cholesterol; they are more effective than statins on triglycerides.
• The advantages of fenofibrate include the uricosuric effect - it reduces the level of uric acid by 10 - 28% due to increased renal excretion of urates.
• Fibrates weaken postprandial hyperlipidemia, especially in patients with type 2 diabetes.

Indications for the appointment of fibrates: IIb phenotype with a high level of TG, remnant III and IV, V types with a high risk of pancreatitis, decreased HDL cholesterol. When using fibrates, ultrasound monitoring of the state of the gallbladder is necessary (increase the lithogenicity of bile).

C10AC Substances that enhance the excretion of bile acids

C10AC01 Cholestyramine

C10AC02 Cholestipol

C10AC03 Colextran

C10AC04 Cogwheels

C10AD Niacin and its derivatives

C10AD01 Niceritrol

C10AD02 Niacin (nicotinic acid)

C10AD03 Nicofuranose

C10AD04 Aluminum nicotinate

C10AD05 Nicotinyl alcohol (pyridylcarbinol)

C10AD06 en: Acipimox

Medicines that are not recommended for use with nicotinic acid preparations due to the risk of side effects:

• statins (risk of hepatotoxicity)
• fibrates (risk of hepatotoxicity and rhabdomyolysis)

Control is necessary ALT, AST, GGTP.

• In patients with diabetes mellitus and gout, an exacerbation of the underlying disease is possible, in this category of patients it is necessary to avoid the appointment of any form of nicotinic acid.

C10AX Other lipid-lowering drugs

C10AX01 Dextrotyroxine

C10AX02 Probucol

C10AX03 Thiadenol

C10AX04 Benfluorex

C10AX05 Meglutol

C10AX06 Omega-3 fatty acids

C10AX07 Magnesium pyridoxal 5-phosphate glutamate

C10AX08 Policosanol

C10AX09 Ezetimibe

In the course of numerous clinical studies using policosanol and statins, data were obtained that the effectiveness of polycosanol and statins to reduce LDL is approximately the same, while polycosanol is much more effective than drugs from the statin group increases HDL . Unlike statins, policosanol has no side effects on other organs and systems of the body. ^{[7] [8] [9] [10]} It is also proved that policosanol helps to reduce to normal levels of alanine aminotransferase (AlAT) and gamma-glutamyltranspeptidase (GGT) ^[11]

C10BA HMG CoA reductase inhibitors in combination with other lipid-lowering drugs

C10BA01 Lovastatin with nicotinic acid

C10BA02 Simvastatin and Ezetimibe

C10BX HMG CoA reductase inhibitors, other combinations

C10BX01 Simvastatin and acetylsalicylic acid

C10BX02 Pravastatin and acetylsalicylic acid

C10BX03 Atorvastatin and amlodipine

• Statins / G. Ya. Schwartz // Big Russian Encyclopedia : [in 35 vols.] / Ch. ed. Yu.S. Osipov . - M .: Great Russian Encyclopedia, 2004—2017.