1.Intensive atorvastatin therapy in patients with acute myocardial infarction.
Lan-feng WANG ; Zhu-qin LI ; Qing TANG ; Wei-min LI ; Shi-ying FU
Chinese Journal of Cardiology 2008;36(7):598-601
OBJECTIVETo assess the safety and efficacy of 40 mg daily atorvastatin in patients with acute myocardial infarction.
METHODSA total of 1102 patients with AMI admitted to our hospital from 2003 to 2007 were assigned to atorvastatin 40 mg daily within 24 hours of hospitalization and continued till 3 months post discharge. Patients with LDL-C < 2.0 mmol/L or increased liver enzyme level (3 times higher than normal) at discharge received atorvastatin 20 mg daily. Lipid profiles, high-sensitivity C-reactive protein, liver enzyme level were measured at admission, hospital discharge and 3 months after discharge.
RESULTS(1)The mean hospitalization duration was (10.17 +/- 1.83) days. LDL-C was continuously decreased [(3.24 +/- 1.04) mmol/L at admission, (2.27 +/- 2.00) mmol/L at discharge and (1.48 +/- 0.78) mmol/L at 3 months after discharge, all P < 0.05]. HDL-C decreased from (1.45 +/- 0.38) mmol/L to (1.20 +/- 0.30) mmol/L at hospital discharge, then increased to (1.65 +/- 1.79) mmol/L at 3 months after hospital discharge (all P < 0.05). TC and apoB were also significantly decreased from admission to discharge (all P < 0.05). (2) high-sensitivity C-reactive protein level significantly decreased from admission to hospital discharge and at 1 months after hospital discharge [(49.71 +/- 50.46) mg/L vs. (8.80 +/- 17.66) mg/L vs. (2.61 +/- 2.30) mg/L, all P < 0.05]. (3) Increased ALT > 120 U/L (3 times higher than normal) were found in 127(11.25%), AST > 120 U/L were found in 26(2.40%) patients at discharge. There were still 4 patients with increased ALT (> 120 U/L) at 1 months after discharge and all returned to normal at 3 months after discharge.
CONCLUSIONIntensive atorvastatin therapy with a dose of 40 mg daily is safe and effective for patients with AMI.
Aged ; Anticholesteremic Agents ; therapeutic use ; Atorvastatin Calcium ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; Pyrroles ; therapeutic use ; Treatment Outcome
2.Use of atorvastatin in lipid disorders and cardiovascular disease in Chinese patients.
Yi-Cong YE ; Xi-Liang ZHAO ; Shu-Yang ZHANG
Chinese Medical Journal 2015;128(2):259-266
OBJECTIVEStatins are still underused for the prevention of cardiovascular disease (CVD) in China. Hence, we conducted a systemic review on the pharmacology, clinical efficacy, and adverse events of atorvastatin, as well as on patient adherence.
DATA SOURCESWe conducted a systemic search in PubMed with the following keywords: "atorvastatin" (Supplementary concept) or "atorvastatin" (All field) and ("China" [AD] or "China" [all field] or "Chinese" [All field]).
STUDY SELECTIONClinical or basic research articles on atorvastatin were included.
RESULTSAtorvastatin is a reversible and competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, decreasing the de novo cholesterol synthesis. The pharmacokinetics of atorvastatin among Chinese is similar to those in Caucasians, and several gene polymorphisms have proved to be associated with the metabolism of atorvastatin in the Chinese population. Several international multiple-center randomized control trials have demonstrated the benefit of atorvastatin for primary and secondary prevention of CVD. None of them, however, included the Chinese, and current evidence in the population is still inadequate, due to the small sample size, low study quality, short study duration, and the use of surrogate endpoints instead of clinical endpoints. The overall incidence of adverse events observed with atorvastatin did not increase in the 10-80 mg dose range, and was similar to that observed with placebo and in patients treated with other statins, which makes atorvastatin well-tolerated in the Chinese population. Moreover, high patient adherence was observed in clinical studies.
CONCLUSIONSBased on the current available evidence, there is no significant difference between Chinese and non-Chinese population in term of pharmacology and clinical efficacy/safety. High-quality evidence is still needed to support the use of atorvastatin in high-risk Chinese population.
Atorvastatin Calcium ; Cardiovascular Diseases ; drug therapy ; China ; Heptanoic Acids ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Pyrroles ; therapeutic use
3.Analysis of clinical use of shuxuening injection in treatment of cerebral infarction based on real world.
Yan-Hua LUO ; Yan-Ming XIE ; Wei YANG ; Yong-Yan WANG ; Li YOU ; Yan ZHUANG
China Journal of Chinese Materia Medica 2014;39(18):3499-3503
To know the characteristics of Shuxuening injection used on cerebral infarction patients in clinical practice, 6 053 cases of Hospital information system (HIS) data from 20 hospitals were analyzed. Using the basic description method and association rules to analysis the data. By analysis the data we found that the average age of cerebral infarction patients who used Shuxuening injection is 67.96, 83.94% of patients were aged 46-80. The injection is administered intravenously,with most patients receiving a dosage of 15-20 mL per dose for between 1 and 14 days. It is always combined with aspirin (48.508%), cinepazide maleate injection (22.073%), atorvastatin calcium tablets (18.873%) in clinical practice. When it comes to two drug combinations, it always combined with cinepazide maleate injection and aspirin (8.178%), nicergoline capsules and aspirin (7.63%). Therefore, based on existing data, we give the conclusion that for the treatment of cerebral infarction Shuxuening injection is mainly used for older patients, and is often combination with similar pharmacological effects chemical drugs, which is complied with the guidelines. However, the wrong dose is still exist, doctors should realize the hiding risk.
Adolescent
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Adult
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Aged
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Aged, 80 and over
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Anticoagulants
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therapeutic use
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Aspirin
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therapeutic use
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Atorvastatin Calcium
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Cerebral Infarction
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drug therapy
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Drugs, Chinese Herbal
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therapeutic use
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Female
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Heptanoic Acids
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therapeutic use
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Humans
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Male
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Middle Aged
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Piperazines
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therapeutic use
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Pyrroles
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therapeutic use
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Young Adult
4.Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial.
Si Yu CAI ; Xiang GU ; Pei Jing LIU ; Rong Shan LI ; Jian Jun JIANG ; Shui Ping ZHAO ; Wei YAO ; Yi Nong JIANG ; Yue Hui YIN ; Bo YU ; Zu Yi YUAN ; Jian An WANG
Chinese Journal of Cardiology 2023;51(2):180-187
Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male
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Humans
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Middle Aged
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Atorvastatin/therapeutic use*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
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Hypercholesterolemia/drug therapy*
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Cholesterol, LDL/therapeutic use*
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Anticholesteremic Agents/therapeutic use*
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Treatment Outcome
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Triglycerides
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Apolipoproteins B/therapeutic use*
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Double-Blind Method
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Pyrroles/therapeutic use*
5.Effect of different doses of atorvastatin on adhesion molecules of the patients undergoing percutaneous coronary intervention.
Qi-lin MA ; Long MO ; Tian-lun YANG ; Xiao-qun PU ; Sheng-bin WU ; Wei XIE ; Xiao-lin ZENG ; Fan CHEN ; Fang-ping CHEN
Journal of Central South University(Medical Sciences) 2006;31(6):914-916
OBJECTIVE:
To determine the effect of different doses of atorvastatin on the serum soluble intercellular adhesion molecules-1 (sICAM-1) in patients undergoing percutaneous coronary intervention (PCI).
METHODS:
The study consisted of 38 patients with unstable angina and 10 patients with old infarction who underwent elected PCI for stenotic lesions of the coronary artery. Patients were randomly assigned to either aggressive group or conventional one. After PCI the patients took atorvastatin 20 mg per day or 10 mg per day. Blood lipid profile was examined before, and 3 months after the PCI. SICAM-1 was examined before the PCI, 48 hours and 3 months after the PCI.
RESULTS:
The total cholesterol and LDL-Cholesterol 3 months after the PCI in the 2 groups were lower than those before the PCI (P<0.01). The aggressive group showed greater reduction in concentrations of TC and LDL-C than the conventional group (P<0.01). The changes in concentrations of HDL-C between pre-PCI and 3 months after the PCI and TG were not obvious (P>0.05). sICAM-1 in the 2 groups 48 hours after the PCI significantly higher than that before the PCI (P<0.01). But sICAM-1 in the 2 groups 3 months after the PCI significantly lower than that before the PCI (P<0.01 or P<0.05). The aggressive group showed greater reduction than the conventional group (P<0.01). TC and LDL-C were positively correlated with sICAM-1(r=0.2413, r=0.2691, all P<0.05).
CONCLUSION
Atorvastatin 20 mg per day reduces TC, LDL-C, and sICAM-1 to a greater extent than atorvastatin 10 mg per day. The effect on sICAM-1 is partly related to reduce lipid profile.
Aged
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Atorvastatin
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Female
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Heptanoic Acids
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administration & dosage
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therapeutic use
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Humans
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Intercellular Adhesion Molecule-1
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blood
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Male
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Middle Aged
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Percutaneous Coronary Intervention
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Pyrroles
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administration & dosage
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therapeutic use
6.Combined effect of atorvastatin and probucol on plasma cystatin C levels and severity of coronary lesion in patients with borderline coronary lesion.
Chang-Jiang GE ; Shu-Zheng LÜ ; Li-Xia FENG ; Yong HUO ; Xian-Tao SONG ; Xin CHEN ; Kang MENG ; Fei YUAN
Chinese Medical Journal 2012;125(14):2472-2476
BACKGROUNDThe plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions.
METHODSOne hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography.
RESULTSPcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment.
CONCLUSIONSCystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.
Aged ; Anticholesteremic Agents ; therapeutic use ; Atorvastatin Calcium ; Coronary Disease ; blood ; drug therapy ; pathology ; Cystatin C ; blood ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Probucol ; therapeutic use ; Prospective Studies ; Pyrroles ; therapeutic use
7.Effects of atorfastatin on the cognitive function of patients with vascular cognitive impairment and different apolipoprotein E genotypes.
Ping GU ; Jian WANG ; Jia-qing SHAO ; Hong DU ; Kai ZHANG ; Wei-min JIANG
Journal of Southern Medical University 2010;30(3):512-514
OBJECTIVETo study the effect of atorfastatin on the cognitive function of patients with vascular cognitive impairment (VCI) and different apolipoprotein E genotypes.
METHODSThe ApoE polymorphism was genotyped by PCR sequencing and the patients were divided into Eepsilon4 carrier (epsilon4+) group (n=24) and epsilon4- group (n=51). All the patients were given 20 mg oral atorfastatin every evening. The indices of TC, TG, HDL-C, LDL-C, as well as the scores of MMSE and clock-drawing test were compared between the two groups before and 24 weeks after the treatment.
RESULTSCompared with those without epsilon4 allele, epsilon4+ patients had obviously increased plasma LDL level and lowered scores of MMSE. Plasma TC, TG and LDL-C were decreased significantly in the two groups after the treatment, and the improvement of TC was greater in patients without epsilon4 allele. The scores of MMSE increased significantly in patients with epsilon4 allele. The improvement in the scores of MMSE and clock-drawing test was greater in epsilon4+ group than in epsilon4- group.
CONCLUSIONAtorfastatin may improve the cognitive function in patients with VCI carrying epsilon4 allele, the effect of which may not be related to lowed blood lipids.
Aged ; Apolipoproteins E ; genetics ; Atorvastatin Calcium ; Cognition Disorders ; drug therapy ; genetics ; Dementia, Vascular ; drug therapy ; genetics ; Female ; Genotype ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Neuroprotective Agents ; therapeutic use ; Pyrroles ; therapeutic use
8.Atorvastatin use and coronary flow reserve in patients with coronary slow flow.
Ying FAN ; Shu-Sen YANG ; Jiang-Bo YU ; Jin-Hong HAO ; Wei HAN ; Run-Tao GAN ; Zheng WANG ; Wei-Min LI ; Yong-Lin HUANG
Chinese Journal of Cardiology 2010;38(2):143-146
OBJECTIVETo investigate the impact of statin use on coronary flow reserve (CFR) in patients with slow coronary flow.
METHODSA total of 91 patients with chest pain and coronary slow flow but normal coronary angiography were included in this study, patients were divided into statin group (atorvastatin 20 mg/d for 8 weeks, n = 51) and non-statin group (n = 40), 26 healthy subjects with normal angiography and negative exercise ECG test served as normal controls. Blood cholesterol was measured. Doppler coronary flow velocity and Doppler reserve measurement of distal left anterior descending were recorded at rest and adenosine infusion (140 microgxkg(-1)xmin(-1)) induced hyperemia state, CFR was calculated by the ratio of maximal hyperemia and baseline peak diastolic coronary flow velocity (hCFV and bCFV) before and after atorvastatin treatment.
RESULTS(1) Eight weeks later, total cholesterol and LDL-C levels were significantly lower in statin group than in non-statin group and control group [TC (3.83 +/- 0.80) mmol/L vs. (5.30 +/- 1.18) mmol/L vs. (5.32 +/- 1.17) mmol/L, P < 0.05; LDL-C (2.26 +/- 0.64) mmol/L vs. (3.28 +/- 0.85) mmol/L vs. (3.30 +/- 0.82) mmol/L, P < 0.05]. (2)Baseline CFR levels were significantly lower in statin group and non-statin group than that in control group (2.32 +/- 0.30 vs. 2.25 +/- 0.33 vs. 3.15 +/- 0.34, P < 0.05). Compared with non-statin group and statin group before treatment, 8 weeks statin treatment was associated with reduced bCFV [(26.06 +/- 3.22) cm/s vs. (29.02 +/- 3.36) cm/s and (26.06 +/- 3.22) cm/s vs. (28.43 +/- 3.40) cm/s, P < 0.05], increased hCFV [(77.63 +/- 8.96) cm/s vs. (65.17 +/- 7.22) cm/s and (77.63 +/- 8.96) cm/s vs. (64.58 +/- 6.26) cm/s, P < 0.05] and increased CFR (3.07 +/- 0.29 vs. 2.28 +/- 0.35 and 3.07 +/- 0.29 vs. 2.32 +/- 0.30, P < 0.05). bCFV, hCFV and CFR of statin group post treatment were similar to those of controls (P > 0.05).
CONCLUSIONPatients with coronary slow flow were associated with lower CFR which could be significantly improved by statin therapy.
Adult ; Aged ; Anticholesteremic Agents ; therapeutic use ; Atorvastatin Calcium ; Coronary Artery Disease ; drug therapy ; physiopathology ; Female ; Fractional Flow Reserve, Myocardial ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Pyrroles ; therapeutic use
9.Treatment of combined hyperlipidemia patients by jiangzhi tongluo soft capsule combined atorvastatin calcium tablet: a clinical study.
Ying XIE ; Yu-Bin HE ; Shi-Xin ZHANG ; Ai-Qun PAN ; Jun ZHANG ; Xiao-Hong GUAN ; Jin-Xue WANG ; Wen-Sheng GUO
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(9):1059-1063
OBJECTIVETo evaluate the efficacy and safety of using Jiangzhi Tongluo Soft Capsule (JTSC) combined with Atorvastatin Calcium Tablet (ACT) or ACT alone in treatment of combined hyperlipidemia.
METHODSA randomized, double blinded, parallel control, and multi-center clinical research design was adopted. Totally 138 combined hyperlipidemia patients were randomly assigned to the combined treatment group (A) and the atorvastatin treatment group (B) by random digit table, 69 in each group. All patients took ACT 20 mg per day. Patients in the A group took JTSC 100 mg each time, 3 times per day. Those in the B group took JTSC simulated agent, 100 mg each time, 3 times per day. The treatment period for all was 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were observed before treatment, at week 4 and 8 after treatment; and safety was assessed as well.
RESULTSAt week 4 and 8 after treatment serum TG decreased by 26.69% and 33.29% respectively in the A group (both P < 0.01), while it was decreased by 25.7% and 22.98% respectively in the B group (both P < 0.01). At week 8 decreased serum TG was obviously higher in the A group than in the B group (P < 0.05). Compared with before treatment, serum levels of LDL-C and TC levels decreased significantly in the two groups (all P < 0.01). There was no statistical difference in the drop-out value and the drop-out rate of serum LDL-C and TC levels (P > 0.05). At week 8 the serum HDL-C level showed an increasing tendency in the two groups. No obvious increase in peptase or creatase occurred in the two groups after treatment.
CONCLUSIONJTSC combined with ACT could lower the serum TG level of combined hyperlipidemia patients with safety.
Adult ; Atorvastatin Calcium ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Hyperlipidemias ; drug therapy ; Male ; Middle Aged ; Pyrroles ; therapeutic use ; Treatment Outcome ; Triglycerides ; blood
10.The effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI.
Shao-hong DONG ; Jun-min WEN ; Lin-jie LUO ; Ke-qi CHEN ; Xin-jian LIANG ; Yi-fu LI ; Hua-dong LIU ; Huan-zhan CHEN ; Zhi-xin HUANG ; Xin JIANG
Chinese Journal of Cardiology 2006;34(4):353-356
OBJECTIVETo assess the safety and effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI.
METHODSA total of 92 patients with ACS post successful PCI were randomly divided into atorvastatin 10 mg/d (group A) and atorvastatin 40 mg/d (group B) on top of the standard medical therapy. Blood were taken at baseline, 4, 12 and 24 weeks for serum alanine aminotransferase (ALT), lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloprotease-9 (MMP-9) measurements. The major adverse cardiac events (MACE) were also observed.
RESULTSThere was no significant difference in medication withdrawn (2 vs. 3 cases) due to increased ALT (3 times higher than normal) and incidence of MACE (5 vs. 7 cases) between the groups. TC and LDL were significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 24 weeks post medication (P < 0.05) while TG and HDL remained unchanged. hs-CRP was significantly reduced at 12 and 24 weeks in both groups compared to baseline and the reduction was more significant in group B than that in group A at 24 weeks. MMP-9 was significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 12 weeks post medication (P < 0.05).
CONCLUSIONBoth atorvastatin doses significantly reduced TC, LDL, hs-CRP and MMP-9 in ACS patients post PCI and the reduction was more significant in high dose atorvastatin group at 24 weeks while the MACE and drug withdraw rates were similar between the groups.
Acute Coronary Syndrome ; blood ; drug therapy ; Alanine Transaminase ; blood ; Angioplasty, Balloon, Coronary ; Atorvastatin Calcium ; C-Reactive Protein ; metabolism ; Heptanoic Acids ; therapeutic use ; Humans ; Hypolipidemic Agents ; therapeutic use ; Matrix Metalloproteinase 9 ; blood ; Prospective Studies ; Pyrroles ; therapeutic use