What Is the Difference Between Rosuvastatin and Simvastatin?

Rosuvastatin Calcium (Rosuvastatin Calcium; Rosuvastatin Calcium; rosuvastatin Calcium; rosuvastatin Calcium; developed in Japan, Shionogi (Osaka Shionogi)), transferred to the British company Zeneca in April 1998, and named rosuvastatin. Phase II, Phase IIa and Phase IIb clinical validation of the drug was completed in the United States in February 1999, and phase III clinical validation was accelerated. In December 2000, AstraZeneca designated Rosuvastatin as Crestortm. From its existing clinical validation results and comparison with similar products, rosuvastatin is worthy of being called a "super statin". Its lipid-lowering effect is very good and it is by far the most powerful lipid-lowering agent. drug. Therefore, the independent research and development of a new statin drug, rosuvastatin, is of great significance to fill the gap in our country's new drugs, promote the health of our people, and achieve social and economic benefits.

Rosuvastatin calcium

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Rosuvastatin Calcium (Rosuvastatin Calcium; Rosuvastatin Calcium; rosuvastatin Calcium; rosuvastatin Calcium; developed in Japan, Shionogi (Osaka Shionogi)), transferred to the British company Zeneca in April 1998, and named rosuvastatin. Phase II, Phase IIa and Phase IIb clinical validation of the drug was completed in the United States in February 1999, and phase III clinical validation was accelerated. In December 2000, AstraZeneca designated Rosuvastatin as Crestortm. From the existing clinical validation results and comparison with similar products, rosuvastatin is worthy of being called "super statin".

Chinese name: rosuvastatin calcium

(+)-(3R, 5S) -7- [4- (4-fluorophenyl) -6-isopropyl-2- (N-methyl-N-methanesulfonylamino) pyrimidin-5-yl] -3,5-Dihydroxy-6- (E) -heptenoate calcium

English name: Rosuvastatin Calcium

English alias: Rosuvastatin Calcium; (3R, 5S, 6E) -7- [4- (4-fluorophenyl) -6- (1-methylethyl) -2- [N-methyl (n-methylsulfonyl) amino] -5-pyrimidinyl ] -3,5-dihydroxy-6-Heptenoic calcium; (3R, 5S, 6E) -7- [4- (4-fluorophenyl) -2- [methyl (methylsulfonyl) amino] -6- (propan-2-yl ) pyrimidin-5-yl] -3,5-dihydroxyhept-6-enoic acid; (6E) -7- {4- (4-fluorophenyl) -6- (1-methylethyl) -2- [methyl (methylsulfonyl) amino ] pyrimidin-5-yl} -3,5-dihydroxyhept-6-enoic acid; calcium (-1) anion; (E) -6- [4- (4-fluorophenyl) -6-isopropyl-2- (methyl- methylsulfonyl-amino) pyrimidin-5-yl] -2,4-dihydroxy-hex-5-enoate

Molecular structural formula: (C22H28FN3O6S) 2Ca

CAS NO.:147098-20-2

Properties: This product is off-white or light yellow powder

Rosuvastatin

The main pharmacological effects are: inhibit the rate-limiting enzyme HMG-CoA reductase in the cholesterol synthase system; increase the low density lipoprotein (LDL) receptor; inhibit the synthesis of very low density lipoprotein cholesterol (VLDL-C); anti-atherosclerosis Like hardening. Compared with similar products, rosuvava can not only reduce the content of low-density lipoprotein (LDL), but also increase the content of high-density lipoprotein (HDL) which is beneficial to the human body by 14% in the factory, which can cause cardiovascular disease The risk is reduced by almost 50%. In reducing LDL-C (very low density lipoprotein cholesterol), rosuvastatin is better than simvastatin and pravastatin; rosuvastatin is used in the treatment of patients with type a or b hyperlipidemia The effect of lowering LDL-C (very low density lipoprotein cholesterol) and increasing HDL-C (high density lipoprotein cholesterol) is better than atorvastatin. In the treatment of patients with heterozygous family genetic hyperlipidemia, Luo Su The effect of vastatin is stronger than atorvastatin. In terms of safety, the effect of rosuvastatin on liver function has not been observed clinically, and there is no significant increase in transaminase; patients with renal insufficiency need to reduce the dose of this medicine. Compared with Pyro's atorvastatin (Lipitor) and Merck's Svastatin (Zocor), 10 mg of rosuvastatin can reduce LDL-C by 60-70%, while 40 mg of atorvastatin It is 40-50%, svastatin is 40%, and rosuvastatin can also increase HDL-C by 14%. It is generally considered at home and abroad that rosuvastatin is the most potential "statin" drug.

At the largest annual meeting of the American College of Cardiology (AHA) in 2003, there were reports of clinical studies of new drugs worthy of attention. For example, AstraZeneca's recently launched statin, rosuvastatin, is called "super statin." Professor Shepherd recently completed a clinical trial comparing the lipid-lowering effects of statins. The results of 8 weeks of medication showed that the compliance rate of rosuvastatin 10mg (n = 539) LDL-C was 80%, while atorvastatin 10mg (N = 529) The compliance rate was 63% (P <0.001), and the atorvastatin 20mg (n = 925) LDL-C compliance rate was 74% (P <0.01). A study by Jones PH showed that rosuvastatin 10mg reduced LDL-C by 46%, while atorvastatin increased from 10mg to 20mg, 40mg, and LDL-C decreased by 37% (P <0.001), 43%, and 48%; Xin When vastatin was increased from 10 mg to 20 mg and 40 mg, LDL-C decreased by 28%, 35%, and 39% (all P values were less than 0.001); when pravastatin was increased from 10 mg to 20 mg and 40 mg, LDL-C was reduced by 20% , 24% and 30% (all P values <0.001)

Indications: Primary hyperlipidemia and other disorders caused by lipids.

I. Introduction to the variety

Cardiovascular disease is a type of disease that seriously endangers human health. In recent years, both in Western and Eastern countries, the morbidity and mortality of this disease have increased significantly. According to statistics from the World Health Organization, there are approximately 15 million people died of cardiovascular and cerebrovascular diseases. In China, the incidence of cardiovascular and cerebrovascular diseases is as high as 8%, and the mortality rate is close to 50% of the total mortality rate. On average, one person died of cardiovascular and cerebrovascular diseases every 20 minutes. Cardio-cerebral vascular disease is mainly caused by atherosclerosis, and more than 80% of atherosclerosis is caused by hyperlipidemia. According to the survey, among those aged 15-69 who have been tested for lipids, 40% are hyperlipidemia.

Hyperlipidemia is a type of systemic lipid that has high cholesterol (TC), triglyceride (TG), and / or low density lipoprotein (LDL) and / or low serum high density lipoprotein (HDL) in serum. Metabolic abnormalities. For more than 20 years, many clinical trials through secondary and primary prevention of coronary heart disease have confirmed that reducing serum low-density lipoprotein cholesterol (LDL-C) can significantly reduce the incidence, mortality and total mortality of cardiovascular disease. In recent years, new statin lipid-lowering drugs have been developed and marketed, which can effectively reduce serum low-density lipoprotein (LDL-C) blood cholesterol. Since 1994, five large-scale clinical studies have been published. (4S, WOSCAPS, CARE, LIPID, AFCAPS / TexsCAPS), the results have consistently confirmed that the application of statin lipid-lowering drugs can significantly reduce plasma cholesterol (mainly LDL-C) levels, and can significantly reduce coronary heart disease patients and non-crown Incidence of coronary events and coronary heart disease mortality without increasing mortality from non-cardiovascular diseases. Therefore, reducing LDL-C has become one of the important measures for the prevention and treatment of coronary heart disease.

Rosuvastatin has the following pharmacological effects:

(1) Inhibition of HMG-CoA reductase HMG-CoA reductase is a rate-limiting enzyme in the cholesterol synthase system. It inhibits HMG-CoA reductase, thereby reducing cholesterol synthesis. Rosuvastatin has biological activity after oral absorption and exerts its effect faster. Rosuvastatin has the strongest inhibitory effect on HMG-CoA reductase among similar drugs.

(2) Increase of low-density lipoprotein (LDL) receptor rosuvastatin reduces the cholesterol concentration in plasma and tissue cells through the inhibition of HMG-CoA reductase, which can stimulate the increase of LDL receptor density in the liver, thereby Increases plasma low-density lipoprotein cholesterol (LDL-C) clearance. The liver LDL receptor can still bind to very low density lipoprotein (VLDL), which can increase the degradation of VLDL, thereby reducing the triacylglycerol concentration.

(3) Inhibition of very low-density lipoprotein cholesterol (VLDL-C) synthesis of cholesterol is necessary for the synthesis of VLDL. Rosuvastatin reduces VLDL synthesis and secretion by reducing plasma cholesterol concentrations. VLDL is necessary for carrying and transporting triacylglycerol, and VLDL-C is the precursor of LDL-C, so it can reduce triacylglycerol, VLDL-C, LDL-C.

(4) Anti-atherosclerotic effects Rosuvastatin is beneficial for delaying atherosclerotic lesions by reducing blood lipids, reducing lipid infiltration and foam cell formation, and also inhibits platelet activation, reduces blood viscosity, and inhibits coagulation. .

Clinical research data: At the 22nd annual meeting of the European Cardiovascular Society, rosuvastatin was called the most powerful new lipid-lowering drug. Dr. Esther Wall, a professor of cardiovascular disease at Leiden University Medical Center in the Netherlands, pointed out that early clinical trials show that rosuvastatin is extraordinary in that it can not only reduce the content of low-density lipoprotein (LDL), but also Increase the content of high-density lipoprotein (HDL) that is good for the human body by 14%, which can reduce the risk of cardiovascular disease by nearly 50%.

(1) Rosuvastatin is better than Simvastatin and Pravastatin in reducing LDL-C (Very Low Density Lipoprotein Cholesterol), so that more patients can achieve the desired LDL-C level: Rosuvastatin Statins have a 65% reduction in LDL-C in clinical validation. In randomized, double-blind, multi-channel clinical trials, rosuvastatin, simvastatin, and pravastatin are used to treat primary hyperlipidemia. The lipid-lowering effect of the disease was compared in 502 patients (18 years of age) with LDL-C levels 160 mg / dL, <250 mg / dL, and triglyceride (TG) levels 400 mg / dL, and were randomly treated for 12 weeks. , The doses were rosuvastatin 5mg / d (n = 120); rosuvastatin 10mg / d (n = 115); pravastatin 20mg / d (n = 137) and simvastatin 20mg / d (n = 130). Therapeutic effect Rosuvastatin 5 and 10 mg doses reduced LDL-C by 42% and 49%, respectively, while pravastatin reduced 28% (p <0.001 compared with two doses of rosuvastatin); simvastatin 37 % (P <0.01 compared with rosuvastatin 5mg, P <0.001 compared with rosuvastatin 10mg). More patients achieved normal LDL-C levels by taking rosuvastatin, returned to normal levels by 87% with rosuvastatin 10mg, rosuvastatin 5mg was 71%, and pravastatin 53%, Xin With vastatin 64%, rosuvastatin has a significantly lower blood lipid effect than pravastatin and simvastatin. The more obvious advantages of rosuvastatin are in the treatment of high-risk patients. The four groups reduced LDL-C levels: rosuvastatin 5mg42%, 10mg 67%, pravastatin 7%, and simvastatin 19%. The therapeutic effects of rosuvastatin 5mg and 10mg can statistically significantly reduce the total cholesterol (TG) and apolipoprotein (apo) B levels, and can significantly mention the lipid ratio (see Table 2). The dose groups are well tolerated, and have a significant effect on reducing TG and increasing HDL-C.

Changes in lipid levels at week 12 (%)

LDL- C HDL- C TC TG ApoB APO A1 APO A1 LDL-C / HDL-C Non-HDL- C / HDL-C Apo B / ApoA1

Rosuvastatin 5mg -421,3 +6 -301,3 -12 -331,4 +7 -451,3 -331,3 -411,3 -371,3

Rosuvastatin 10mg -491,2 +7 -341,2 -18 -391,2 +5 -511,2 -381,2 -471,2 -421,2

PRA 20mg -28 +4 -20 -13 -21 [phone]

SIM 20mg -37 +4 -26 -14 -29 [phone]

1p <0.001vs PRA; 2p <0.001vs SIM; 3p <0.01vs SIM; 4p <0.05 vs SIM

Conclusion: The rosuvastatin 5 and 10 mg doses are significantly better than those of pravastatin 20 mg and simvastatin 20 mg in the treatment of hyperlipidemia patients, so that more patients can reach the desired normal level of LDL-C.

(2) In the treatment of patients with type a or b hyperlipidemia, rosuvastatin lowers LDL-C and increases HDL-C effect than atorvastatin: 516 patients with primary hyperlipidemia (age 18 years), (LDL-C 160, and <250mg / dL; triglyceride (TG) <400mg / dL), multicenter, randomized, double-blind, placebo-controlled trials were conducted at 6 weeks After the normal diet period, patients received once-daily placebo, atorvastatin, or rosuvastatin 5 mg, 10 mg for 12 weeks. The percentage changes in lipid levels and various lipid parameters after 12 weeks of treatment are shown in the table below:

N TC LDL-C Apo B TG HDL-C Apo AI

Placebo 132 0 (1) 0 (1) +4 (1) -1 (2) +4 (1) +3 (1)

ATV 10mg 127 -25 (1) -35 (1) -26 (1) -19 (2) +8 (1) +3 (1)

ZD 5mg 128 -28 (1) a, d -40 (1) a, c -31 (1) a, c -17 (3) a, ns +13 (1) a, c +7 (1) a, d

ZD 10mg 129 -30 (1) a, b -43 (1) a, b -33 (1) a, b -19 (3) a, ns +12 (1) a, d +7 (1) a, d

ap <0.001 vs placebo; bp <0.001 vs ATV; cp <0.01 vs ATV; dp <0.05 vs ATV; no significant difference in ns vs 84% of patients in the ATV ZD group reached normal LDL-C levels, and atorvastatin 73%. The difference in treatment is obvious, and the effect of ZD is more obvious when treating high-risk patients, reducing the patient's LDL-C level to less than or equal to 100mg / dL. 19%. The above data shows that rosuvastatin, 5 and 10 mg are more effective than atorvastatin 10 mg in reducing LDL-C, TC, Apo B and increasing LDL-C, Apo AI levels.

(3) Rosuvastatin is more effective than atorvastatin in treating patients with genetic hyperlipidemia in heterozygous families: Genetic heterolipidemia in heterozygous families is a common genetic disease that can cause congenital heart disease (HeFH) . The trial compared the effects of rosuvastatin and atorvastatin on HeFH. Clinical comparison trials were conducted in 58 centers around the world using a randomized, double-blind, parallel control group, high-dose method. The subjects were HeFH patients older than 18 years, with an average fasting LDL-C of 220 mg / dL (5.69 mmol / L) or more, less than 500 mg / dL (12.93 mmol / L), and fasting triglycerides (TG) of less than 400 mg / dL (4.452 mmol / L). After a 6-week normal diet period, rosuvastatin (n = 435) or atorvastatin (n = 187) treatments were performed randomly daily based on body weight. The initial dose was 20 mg / d, 40 mg / d after six weeks, and then increased to 80 mg / d after six weeks (18 weeks in total). Clinical results showed that compared with atorvastatin, rosuvastatin reduced LDL-C, TC, ApoB, and increased HDL-C and ApoAI (p <0.001) (see Table 4). In all respects, the LDL-C / HDL-C ratio of the rosuvastatin group was 20% stronger than that of atorvastatin. Both drugs have similar side effects.

% Reduction 1, 2% lipid levels are normal

LDL- C HDL- C TC TG Apo B Apo AI LDL-C / HDL-C All groups 2 High-risk group 3

Rosuvastatin 20/40 / 80mg / d -58 * + 12 * -46 * -28ns -50 * + 6 * -62 * 61 24

Avastatin 20/40 / 80mg / d -50 [phone]

118-week data; 2 rosuvastatin n = 435, atorvastatin n = 187; 3 rosuvastatin n = 134, atorvastatin n = 63; * p <0.001 vs atorvastatin; no significant difference in ns .

Test data show that rosuvastatin can significantly reduce LDL-C and increase HDL-C levels, and is better than atorvastatin.

(4) The clinical lipid-lowering effects of rosuvastatin and other statins are as follows:

Comparison of lipid-lowering effects of rosuvastatin and other statins (%)

Project TC LDL-C TG HDL-C

Rosuvastatin (5 ~ 10mg.d-1) -32 -49 -18 +14

Lovastatin (20 ~ 40 mg.d-1) -21 -29 -8 +7

Pravastatin (20 ~ 40 mg.d-1) -16 -23 -3 4

Atorvastatin (10 ~ 20 mg.d-1) -30 -38 -21 +8

Simvastatin (10 ~ 20 mg.d-1) -25 -33 -12 +5

Safety evaluation: No effect of rosuvastatin on liver function was observed clinically, and no significant increase in transaminase was observed. Patients with renal insufficiency do not need to reduce the dose of this medicine, and mild liver insufficiency needs to reduce the dose of this medicine.

In summary, rosuvastatin is a new type of HMG-CoA reductase inhibitor, which is effective in reducing serum TC and TG, and its effect is more than that of atorvastatin,