Dyslipidemia is a common metabolic disease in modern people. Most of them are caused by many obstacles in the process of lipoprotein metabolism, lipoprotein metabolism disorder, and a large number of middle-aged and elderly patients. Lipid disease itself is not frightening, the most worrying is that dyslipidemia is currently recognized as an extremely important risk factor for atherosclerosis and coronary heart disease. Fortunately, nature has given human a rich gift-statins.
Development of statins
In 1976, biochemists of Sankong Pharmaceutical Company of Japan accidentally extracted mevastatin from the fungal culture medium, which can inhibit the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) in cholesterol synthesis, thus reducing cholesterol synthesis by 50%. Sadly, mevastatin failed because of an animal safety test, and the otherwise smooth clinical trial came to an abrupt end, and the father of the statins fell. Sometimes the key to the success of a new drug may be a simple chemical group-methyl. Lovastatin, with only one methyl group more than mevastatin, miraculously passed the animal safety test, pushing all the way to the market, saving itself and saving the entire statins market. Subsequently, Pravastatin, Simvastatin, Fluvastatin, Rosuvastatin, Atorvastatin, Pravastatin and so on went on the market one after another, ushering in a new era of lipid-lowering therapy and cardiovascular prevention. The use of statins reduced the mortality of cardiovascular diseases by 20% ~ 30% as a whole. But in recent years, the spotlight of statins has been shining on “big family products” such as Atova and Ritual. Pitching is relatively low-key, but because of the low dose, strong enzyme selectivity, good tolerance, safety, and other clinical advantages, the future potential is great.
- Low dose contains a lot of energy.
There are a lot of research results on the clinical efficacy of Pravastatin, compared with other statins, low dose of Pravastatin can effectively reduce low-density lipoprotein, LCL-C, and has a good effect of increasing high-density lipoprotein, HDL-C, this multi-effect, it not only ensures the reduction of blood lipid but also reduces the cumulative incidence of cardiovascular and cerebrovascular diseases.
- Combination of drugs is more reassuring.
A cross-sectional study of 2742 outpatients with dyslipidemia treated with statins in Switzerland assessed potential severe drug interactions and the occurrence of drug-related effects associated with statins. The use of statins metabolized by CYP450 3A4 significantly increases the likelihood of drug interaction. Even in Lipitor’s instructions, the FDA emphasized that “Atto vastatin is mainly metabolized by CYP450 3A4, combined with CYP450 3A4 strong inhibitors, resulting in drug interaction and increasing adverse effects of skeletal muscle.” However, Pravastatin does not have this problem and is safe when combined with drugs.
- Glucose metabolism has little effect and there is no need to worry about the risk of diabetes.
Studies have shown that Atto vastatin above 20mg can significantly increase fasting plasma insulin and HbA1c levels. However, after the replacement of Pravastatin, the level of glycosylated hemoglobin in the patients decreased significantly.
The 2018 Circulation magazine recently published the largest lipid-lowering study (REAL-CAD study) in Asia to date, sharing new evidence on the efficacy and safety of Pravastatin in Asia. It has been proved that Pravastatin is a new type of statins which can reduce the risk of cardiovascular events and improve the long-term prognosis of patients with coronary heart disease, but does not show an increased risk of new diabetes.
- It is more suitable for the special population of “one old and one small”.
The results of a study of elderly patients with dyslipidemia showed that long-term Pravastatin treatment (2 and 4 mg) could effectively reduce LDL-C levels and had good safety and tolerance in elderly patients. In a study of the efficacy and safety of Pravastatin in the treatment of hyperlipidemia in children and adolescents, up to 4 milligrams of Pravastatin was well tolerated and effective in children and adolescents aged 6 to 17 years. There are no obvious security issues.
Fig 3. Statins structure.
The structure of statins can be divided into three parts: part A, a β, δ-hydroxy valeric acid structure similar to that of HMG in HMG-CoA, the substrate of statins; Part C, a hydrophobic rigid plane structure combined with a hydrophobic shallow ditch produced by enzyme modification; part B, The connection between the two is shown in fig.3. A schematic diagram of the lovastatin and Pravastatin structures in part A is shown in fig.4. The side chains of most statins are 3, 5-dihydroxyheptenic acid or its lactone structure. Lactone structure can be hydrolyzed into open chain carboxylic acid in vivo, thus playing a pharmacological role.
Fig 4. Side chain structure of mother ring of Pravastatin and lovastatin
Conclusion and prospect
Among all the hyperlipemia drugs, statins are the largest hyperlipemia drugs in the market at present, which have the advantages of high target selectivity, definite curative effect, and less side effects. Among so many me-too statins, pravastatin has shown excellent results in drug efficacy, safety, and so on. Although the sales of Pilar have not been able to catch up with Atova and Ritual, in the future with the completion of the consistency evaluation of some high-quality enterprises, it will jointly enhance the market scale of Pilar, and the top C position is just around the corner.
References
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2. Saito, Y., Yamada, N., Teramoto, T., Itakura, H., Hata, Y., Nakaya, N., … & Goto, Y. (2002). A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis, 162(2), 373-379.
3. Nilsson, P. M. (2013). The Role of Statins in the Metabolic Syndrome. In The Metabolic Syndrome(pp. 147-153). Springer, Vienna.