辛伐他汀对冠心病的抗炎作用

目的 :观察辛伐他汀对冠心病病人C反应蛋白 (CRP)、肿瘤坏死因子α(TNF α)、白细胞介素6 (IL 6 )和白细胞介素 8(IL 8)的抑制效应。方法 :冠心病病人 6 0例 ,分为辛伐他汀组和对照组 ,每组30例。对照组给予阿司匹林泡腾片、培哚普利、美托洛尔等治疗 ,辛伐他汀组在此基础上服用辛伐他汀 2 0mg ,po ,qn。疗程均 8wk。结果 :治疗后辛伐他汀组血清中CRP ,TNF α ,IL 6和IL 8浓度明显降低 [(5 .0±s 0 .6 )mg·L- 1vs (3.7± 0 .6 )mg·L- 1,(6 .4± 1.4 )ng·L- 1vs (5 .6± 1.4 )ng·L- 1,(4.4± 1.2 )ng·L- 1vs (4.2± 1.2 )ng·L- 1,(2 8±7)ng·L- 1vs (2 7± 7)ng·L- 1,P <0 .0 5或P <0 .0 1],而对照组则无明显改变 (P >0 .0 5 )。结论 :辛伐他汀能够降低冠心病病人血清中CRP和炎症因子 ,显示其抗炎作用     

吗啡和芬太尼对人外周血肿瘤坏死因子-α和白细胞介素-6表达的影响

目的 :研究吗啡和芬太尼对人外周血肿瘤坏死因子 α(TNF α)和白细胞介素 6(IL 6)表达的影响并探讨其机制。方法 :试验分单独药物组 (A1:吗啡 2 0 0mg·L-1,A2 :吗啡 2mg·L-1,A3 :芬太尼 2mg·L-1和A4:芬太尼 2 0 μg·L-1)、激活组〔A1,A2 ,A3 和A4组加入脂多糖 (LPS) ,称为B1,B2 ,B3 和B4组〕和对照组 (C1:空白对照和C2 :LPS对照 ) ,共 1 0组。检测 7份正常人血标本。用ELISA检测TNF α和IL 6含量。结果 :A组TNF α浓度为 1 84～2 5 1ng·L-1;IL 6为 3 96～ 490ng·L-1。与C1组 (TNF α:2 79ng·L-1;IL 6:5 61ng·L-1)比较 ,差异无显著意义 (P >0 .0 5 )。B组TNF α浓度为 3 5 7～5 3 4ng·L-1;IL 6为 72 0～ 1 3 1 0ng·L-1,明显低于C2 组(TNF α:1 2 2 6ng·L-1;IL 6:1 5 63ng·L-1) (P <0 .0 5 ;P <0 .0 1 ) ,且高剂量组低于其低剂量组。结论 :吗啡和芬太尼不影响静息状态下TNF α和IL 6的表达 ,但可抑制LPS诱导的TNF α和IL 6表达 ,且具有明显量效关系     

肾炎患者外周血单个核细胞尿激酶型纤溶酶原激活剂受体及相关细胞因子的表达

目的　探讨肾炎患者外周血单个核细胞尿激酶受体及相关细胞因子的表达。方法　采用流式细胞术测定肾炎患者外周血单个核细胞尿激酶型纤溶酶原激活剂受体、IL - 2R和整合蛋白 β2 水平 ,双抗体夹心ELISA法测定血清IL - 2 ,IL - 4和IL - 10水平。结果　肾炎患者外周血单个核细胞尿激酶型纤溶酶原激活剂受体、IL - 2R和整合蛋白 β2 表达水平分别为 (15 .94± 3.2 1) %、(10 .93± 4.2 4) %和 (12 .87± 4.79) % ,均显著高于正常组的 (4.2 1± 1.0 2 ) %、(1.49± 0 .47) %和 (2 .0 8± 1.0 1) % (P <0 .0 1) ;血清IL - 2和IL - 4水平分别为 (2 1.14± 8.2 4) μg/L和 (43.5 6± 10 .2 4) μg/L ,亦均显著高于正常组的 (8.73± 4.0 2 ) μg/L和 (2 3.0 4± 4.78) μg/L(P <0 .0 1) ;IL - 10水平 (8.34± 2 .0 1) μg/L则显著低于正常组的 (12 .0 1± 2 .34 ) μg/L(P <0 .0 1) ;89例肾炎患者外周血单个核细胞尿激酶型纤溶酶原激活剂受体表达水平随病情好转而逐渐恢复正常 ,13例患者激素治疗 2周病情无缓解 ,但外周血单个核细胞尿激酶型纤溶酶原激活剂受体表达水平也逐渐恢复。结论　肾炎患者外周血单个核细胞尿激酶型纤溶酶原激活剂受体表达水平与多种细胞因子有关 ,参与肾小球肾炎的发病 ,在肾小球基底膜?     

硝酸异山梨酯静脉滴注对冠心病病人血管内皮功能的影响

目的 :观察硝酸异山梨酯静脉滴注对冠心病病人血管内皮功能的影响。方法 :6 4例冠心病病人随机分为 2组 ,硝酸异山梨酯组 (32例 )予硝酸异山梨酯 2 0mg ,iv ,gtt,qd ;复方丹参组 (32例 )予复方丹参 2 0mL ,iv ,gtt ,qd。均连续用药 4wk。结果 :硝酸异山梨酯组治疗后 6 酮前列腺素F1α(99± 6 9)ng·L- 1]、一氧化氮 [(134± 88) μmol·L- 1]均较治疗前 [(75± 5 8)ng·L- 1,(91± 85 ) μmol·L- 1]上升 ,血组织型纤溶酶原激活物抑制物 [(0 .6 4± 0 .2 7)×10 3AU·L- 1vs (0 .5 4± 0 .2 4 )× 10 3AU·L- 1]、凝血烷B2 [(111± 2 31)ng·L- 1vs (71± 14 6 )ng·L- 1]、内皮素 1[(98± 6 2 )ng·L- 1vs (80± 4 7)ng·L- 1],浓度均下降 (P <0 .0 5 ,P <0 .0 1)。复方丹参组无此变化 (P >0 .0 5 )。结论 :硝酸异山梨酯静脉滴注可改善冠心病病人血管内皮功能     

卡维地洛对87例充血性心力衰竭病人血浆细胞因子的影响

目的 :探讨卡维地洛对充血性心力衰竭(CHF)病人血浆细胞因子的影响。方法 :将 87例CHF病人随机分为常规组和卡维地洛组 ,常规组给予常规抗心力衰竭治疗 ,卡维地洛组在常规基础上按双周剂量递增方案加用卡维地洛口服 ,目标剂量2 5mg ,bid ,治疗 6mo。测定血浆肿瘤坏死因子α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )及心功能 ,以健康人作对照。结果 :CHF病人上述细胞因子均高于健康组 (P <0 .0 1) ,治疗 6mo后卡维地洛组TNF α和IL 6降低 ,治疗前后分别为(4 6±s 18)和 (31± 15 )ng·L- 1,(35± 13)和 (15± 9)ng·L- 1,IL 10升高 ,分别为 (15± 6 )和 (2 4± 7)ng·L- 1(P <0 .0 1) ,TNF α/IL 10降低 ,心功能改善(P <0 .0 1)。结论 :卡维地洛降低炎性细胞因子、增加抗炎性细胞因子水平的这种免疫调节作用可能是其对CHF有益作用的机制之一     

重组人粒细胞集落刺激因子注射液动员外周血干细胞10例

目的 :探讨重组人粒细胞集落刺激因子(rhG CSF)注射液动员外周血造血干细胞 (PBSC)的效果。方法 :对 6例恶性血液病病人 ,1d内静脉注射长春新碱 1～ 2mg·m- 2 及环磷酰胺 4～ 7g·m- 2 (分 4次 ,间隔 4h) ,外周血白细胞降至 1×10 9·L- 1以下时 ,加rhG CSF 6～ 8μg·kg- 1,皮下注射 ,qd× 5～ 7d ;对 4例健康供者在采集PBSC前 5d予rhG CSF 6～ 8μg·kg- 1,皮下注射 ,qd× 5d。白细胞升至 10× 10 9·L- 1以上时采集PSBC ,并进行CD+ 34 及粒 巨噬细胞集落形成单位 (CFU GM )检测。结果 :一次收集单个核细胞计数 (3.9±s 1.7)×10 8·kg- 1;CD+ 34 (4 .8± 2 .3)× 10 8·kg- 1;粒 巨噬细胞集落形成单位 (5± 3)× 10 4 ·kg- 1。未出现严重不良反应。结论 :rhG CSF无论对病人自体还是对健康供者均能安全、高效地动员PBSC ,满足移植所需要。     

氨氯地平在心衰治疗中对肿瘤坏死因子-α、白细胞介素-1,6的作用

目的 :探讨氨氯地平在心力衰竭 (心衰 )治疗中对细胞因子的作用。方法 :选择扩张型心肌病和缺血性心脏病心衰病人共 6 0例 ,随机分成常规组与氨氯地平组。常规组给予常规抗心衰治疗 ,氨氯地平组在常规治疗基础上加用氨氯地平 5mg ,po ,qd。同时建立正常组。检测肿瘤坏死因子 α(TNF α)、白细胞介素 1(IL 1)、白细胞介素 6 (IL 6 )。结果 :IL 1,IL 6 ,TNF α在心衰病人中分别达 (30±s 13) ,(99± 4 3)和 (2 4± 5 )ng·L- 1,较正常人[(6 .1± 1.7) ,(2 9± 8) ,(16± 5 )ng·L- 1]明显增高(P <0 .0 1)。治疗 6wk后 ,氨氯地平组病人较常规组IL 6 ,TNF α明显降低 ,分别为 (45± 2 4 )和 (17±5 ) ,(6 0± 31)和 (2 0± 4 )ng·L- 1(P <0 .0 1)。结论 :氨氯地平治疗心衰的作用之一可能在于降低细胞因子如IL 6和TNF α的水平     

氟伐他汀与普伐他汀治疗高脂血症疗效比较

目的 :观察并比较氟伐他汀与普伐他汀的降脂疗效。方法 :氟伐他汀组 4 1例 (男性 2 2例 ,女性 19例 ,年龄 6 0a±s 8a) ,应用氟伐他汀 2 0～ 4 0mg ,po ,qn× 4wk。普伐他汀组 35例 (男性 2 0例 ,女性 15例 ,年龄 6 0a± 6a) ,应用普伐他汀 10mg ,po ,qn× 4wk。结果 :氟伐他汀降低TC的总有效率 92 % ,普伐他汀为 70 % (P <0 .0 5) ;氟伐他汀降低TG及升高HDL C的总有效率为 6 1%和 6 1% ,与普伐他汀的 73%和 6 9%相似 (P >0 .0 5)。 2组的不良反应发生率为 2 0 % (8/41)和 2 0 % (7/35)。结论 :氟伐他汀是一种安全、有效的降脂药物 ,且降低TC作用优于普伐他汀。     

罗伐他汀钙

罗伐他汀 (ｒｏｓｕｖａｓｔａｔｉｎ)是具有慢结合动力学和高亲和力 (Ｋｉ 值约为 0 .1ｎｍｏｌ·Ｌ- 1)的ＨＭＧ ＣｏＡ还原酶竞争性抑制剂。与其他的他汀类酶抑制剂比较 ,罗伐他汀 (ＩＣ50 =5 0ｎｍｏｌ·Ｌ- 1)与阿托伐他汀(ａｔｏｒｖａｓｔａｔｉｎ)、西立伐他汀 (ｃｅｒｉｖａｓｔａｔｉｎ)、辛伐他汀(ｓｉｍｖａｓｔａｔｉｎ) (ＩＣ50 =8～ 11ｎｍｏｌ·Ｌ- 1)的效果相当 ,比氟伐他汀 (ｆｌｕｖａｓｔａｔｉｎ)、普伐他汀 (ｐｒａｖａｓｔａｔｉｎ) (ＩＣ50 =2 8～ 4 4ｎｍｏｌ·Ｌ- 1)效果更好。将 37名健康男性志愿者分成 3组 ,进…     

芬太尼对人外周血NF-κB活性的影响

目的　验证芬太尼是否影响免疫炎症反应中的某些因素 ,如同吗啡。方法　外周血取自 7个正常志愿者 ,实验分为正常对照组、芬太尼 ( 2 0 μg·L-1和 2mg·L-1)组、模型组(脂多糖 ,LPS组 )和治疗组 (芬太尼 2 0 μg·L-1+LPS、芬太尼 2mg·L-1+LPS)。用流式细胞术检测人外周血中性粒细胞和单核细胞中核因子(NF κB)活性 ,用ELISA检测血清中肿瘤坏死因子 α(TNF α)和白介素 6(IL 6)含量。结果　芬太尼组NF κB活性及TNF α和IL 6含量与正常对照组比较 ,均无明显差异 (P >0 .0 5 )。治疗组 (芬太尼 2 0 μg·L-1+LPS、芬太尼 2mg·L-1+LPS)中NF κB的活性分别为 81 .9% ,76.1 % (中性粒细胞 )和 78.6% ,72 .6%(单核细胞) ,明显低于模型组 88.9%和 85 .1 % (P <0 .0 1 )。TNF α含量在治疗组 (芬太尼 2 0 μg·L-1+LPS、芬太尼 2mg·L-1+LPS)为 45 9和 3 5 7ng·L-1,IL 6为 796和 72 0ng·L-1,两者均低于模型组 (其中TNF α为 1 2 2 6ng·L-1,IL 6为 1 5 63ng·L-1) (P <0 .0 1 )。结论　芬太尼对NF κB的活性及TNF α和IL 6的含量无影响 ,但可抑制LPS诱导的NF κB的活性及TNF α和IL 6的含量 ,且高剂量芬太尼的抑制作用大于低剂量芬太尼的作用     

普伐他汀对急性冠状动脉综合征患者血清TNF-α和IL-6水平的影响

目的 探讨普伐他汀对急性冠状动脉综合征(ACS)患者血清肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)水平变化的影响.方法 将ACS患者50例随机分为普伐他汀组25例和常规治疗组25例,分别于治疗前及治疗4周后行血清TNF-α及IL-6检测,均采用放射免疫分析方法.另选同期健康体检的20例作为对照组.结果 ACS组治疗前血清IL-6、TNF-α水平均明显高于对照组(均P<0.01).普伐他汀组治疗后血清IL-6、TNF-α水平均明显低于治疗前,但仍高于对照组(均P<0.05).常规治疗组患者治疗后血清IL-6、TNF-α降低不明显(P>0.05).结论 IL-6、TNF-α水平升高与ACS发病密切相关,普伐他汀可降低ACS患者血IL-6、TNF-α水平,具有减轻病变部位炎性反应和保护内皮细胞的作用.     

辛伐他汀和普伐他汀对急性冠状动脉综合征患者血脂及C反应蛋白的影响

目的 观察辛伐他汀一日40 mg强化降脂治疗与普伐他汀一日20 mg常规治疗对急性冠状动脉综合征(ACS)患者血脂及C反应蛋白(CRP)水平的影响.方法 选择我院2006年1月-2007年6月ACS住院患者96例,随机分为普伐他汀组(n=46)和辛伐他汀组(n=50),晚间一日1次口服普伐他汀20 mg或辛伐他汀40 mg,疗程4周,测定患者治疗前及治疗后血脂及CRP水平,同时观察药物不良反应.结果 治疗前两组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及CRP水平分别为(5.02±0.85)mmol/L、(1.74±1.52)mmol/L、(2.63±0.36)mmol/L、(1.19±0.05)mmol/L、(12.49±9.02)mg/L和(4.90±1.25)mmol/L、(1.64±1.29)mmol/L、(2.62±0.47)mmol/L、(0.95±0.05)mmol/L、(12.67±17.97)mg/L,组间相比无显著差异(P>0.05).治疗后两组上述指标分别为(4.50±0.89)mmol/L、(1.55±0.28)mmol/L、(2.36±0.39)mmol/L、(1.12±0.06)mmol/L、(3.11±9.33)mg/L和(4.11±0.50)mmol/L、(1.45±0.22)mmol/L、(2.04±0.24)mmol/L、(0.94±0.09)mmol/L、(1.70 1.42)mg/L,其中TC、LDL-C和CRP水平均较治疗前显著下降,且辛伐他汀组与普伐他汀组相比,前者TC、LDL-C和CRP水平下降更为显著(P<0.05).两组患者均未出现非可逆性严重不良反应.结论 与普伐他汀一日20 mg相比,辛伐他汀一日40 mg强化降脂治疗不仅能显著降低TC和LDL-C,而且能显著降低CRP,从而使ACS患者获益更多.     

Effects of C-reactive Protein and Homocysteine on Cytokine Production: Modulation by Pravastatin

Objective.  C-reactive protein (CRP) and homocysteine are markers of cardiovascular risk that may have inflammatory effects. HMG coenzyme A reductase inhibitors (statins) have anti-inflammatory effects in vitro, but it is not clear if such responses in vivo are secondary to lipid lowering. We examined the hypothesis that CRP and homocysteine would stimulate cytokine release in human whole blood and that short-term treatment with a statin would inhibit it.
Methods.  The time course of IL-6 and MCP-1 production was determined in whole blood incubated with saline, 1 µg/mL lipopolysaccaride (LPS), 50 and 100 µM/L DL-homocysteine, and 5 µg/mL human recombinant CRP for 24 hours at 37°C under 5% CO₂ atmosphere. Cytokine responses were determined in blood drawn from 15 healthy volunteers before and after administration of pravastatin 40 mg daily for 2 days.
Results.  Both human recombinant CRP and LPS significantly increased the production of IL-6 and MCP-1 in whole blood samples more than 4-fold ( P  < 0.001) but homocysteine did not. Oral administration of pravastatin, 40mg daily for 2 days, decreased CRP-stimulated IL-6 production by approximately 20% ( P  = 0.02) 6 hours after incubation, but did not affect MCP-1 production ( P  = 0.69). Pravastatin treatment did not affect LPS-stimulated MCP-1 but increased IL-6 modestly.
Conclusions.  CRP stimulated the production of the proatherogenic mediators MCP-1 and IL-6 in human whole blood, but homocysteine did not. CRP-stimulated production of IL-6, but not MCP-1, was modestly attenuated by short-term treatment with pravastatin.     

Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes.

The effects of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin on the contents of cytochrome p450 mRNAs were examined in primary cultures of human hepatocytes prepared from three different livers. Treatment of 2- to 3-day-old human hepatocyte cultures with 3 x 10(-5) M lovastatin, simvastatin, fluvastatin, or atorvastatin for 24 h increased the amounts of CYP2B6 and CYP3A mRNA by an average of 3.8- to 9.2-fold and 24- to 36-fold, respectively. In contrast, pravastatin treatment had no effect on the mRNA level of either CYP2B6 or CYP3A, although treatment with pravastatin did produce the expected compensatory increase in HMG-CoA reductase mRNA content, indicating effective inhibition of cholesterol biosynthesis. Although treatment with the active (+), but not the inactive (-), enantiomer of atorvastatin increased the amount of HMG-CoA reductase mRNA, treatment with each enantiomer significantly induced both CYP2B6 and CYP3A mRNA levels. Treatment of primary cultured rat hepatocytes with the atorvastatin enantiomers effectively increased the amount of CYP3A mRNA, but had no effect on CYP2B or CYP4A mRNA levels, in contrast to fluvastatin, which increased both. Findings for p450 proteins by Western blotting were consistent with the mRNA results. These findings indicate that the ability of a drug to inhibit HMG-CoA reductase activity does not predict its ability to produce p450 induction in primary cultured human hepatocytes, and demonstrate that some, but not all, of the effects of these drugs that occur in primary cultured rat hepatocytes are conserved in human hepatocyte cultures.     

普伐他汀对慢性心力衰竭患者心功能及血清C反应蛋白的影响

目的 探讨普伐他汀对慢性心力衰竭(CHF)患者心功能及血清C反应蛋白(CRP)水平的影响.方法 90例CHF患者随机分为他汀组(45例)和对照组(45例).他汀组在常规治疗基础上加用普伐他汀40mg/d;对照组常规治疗.两组患者治疗前、治疗后3个月检测血清CRP及行超声心动图检查测定左心室射血分数(LVEF).结果 两组患者治疗3个月后与治疗前比较,TC、血清CRP水平均有不同程度降低,且他汀组血清CRP水平较对照组明显下降[(15.47±9.83)mg/L,(20.31±7.15)mg/L,P<0.05],LVEF较对照组明显上升[(45.70±7.01)%,(38.34±5.31)%,P<0.05];血清CRP水平与LVEF呈负相关(r=-0.495,P<0.05).结论 普伐他汀能改善CHF患者的预后;血清CRP水平可作为治疗CHF的一个灵敏观察指标.     

Interactions between cell death induced by statins and 7-ketocholesterol in rabbit aorta smooth muscle cells

BACKGROUND AND PURPOSE: 7-Ketocholesterol, an oxysterol present in atherosclerotic lesions, induces smooth muscle cell (SMC) death, thereby destabilizing plaques. Statins protect patients from myocardial infarction, though they induce SMC apoptosis. We investigated whether statins and 7-ketocholesterol exerted additive cell death effects. EXPERIMENTAL APPROACH: Cultured rabbit aorta SMCs (passage 2-6) were exposed to 7-ketocholesterol with or without fluvastatin, simvastatin or pravastatin. Uptake of neutral red (NR), monolayer protein, cleavage of the pan-caspase substrate Asp-Glu-Val-Asp-rhodamine110, cell morphology (light and electron microscopy) and processing of microtubule-associated protein 1 light chain 3 (LC3, immunoblot) were determined. KEY RESULTS: NR uptake declined upon 18 h exposure to 25 microM 7-ketocholesterol (-41+/-3%, n=13), 100 microM fluvastatin (-59%) or 30-100 microM simvastatin (-28 to -74%). Oxysterol and high statin concentrations exerted additive effects, but lower concentrations (fluvastatin 10-30 microM, simvastatin 1-10 microM) partly reversed viability loss. 7-Ketocholesterol caused intense cytoplasmic vacuolization, processing of LC3-I to LC3-II, but little caspase activation (increase 29.5%). Fluvastatin (10-100 microM, 70-545% increase) and simvastatin (3-100 microM 43-322% increase) induced caspase activation without LC3 processing, but failed to activate caspases in 7-ketocholesterol-treated SMCs. Pravastatin up to 100 microM was always inactive. CONCLUSIONS AND IMPLICATIONS: 7-Ketocholesterol caused SMC death, mainly via autophagic vesicle formation with LC3 processing, whereas lipophilic statins evoked SMC apoptosis. Cell death following 7-ketocholesterol and low statin concentrations were not additive, presumably because the autophagic process interfered with statin-induced caspase activation. This further illustrates that drug effects in normal SMCs are not necessarily predictive for activities in atherosclerotic settings.     

瑞舒伐他汀和辛伐他汀对急性冠状动脉综合征患者炎性因子和心血管事件的影响

目的探讨瑞舒伐他汀和辛伐他汀对急性冠状动脉综合征(ACS)患者高敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)和心血管事件的影响。方法选择80例ACS患者分为瑞舒伐他汀组和辛伐他汀组各40例,在常规ACS治疗基础上,分别给予瑞舒伐他汀10 mg/d或辛伐他汀20 mg/d,观察5个月。测定两组患者血清hs-CRP和IL-6水平并观察对比心血管事件发生率。结果治疗后两组血清hs-CRP和IL-6水平均显著降低(t=6.75、6.34,4.32、4.12,P<0.05),瑞舒伐他汀治疗后显著低于辛伐他汀组(t=3.15、3.11,P<0.05)。心血管事件发生率方面瑞舒伐他汀组略低于辛伐他汀组,二者比较,差异无统计学意义(χ2=1.112,P>0.05)。结论瑞舒伐他汀和辛伐他汀均具有显著抗炎作用,都能明显减少心血管事件的发生,瑞舒伐他汀抗炎作用更显著。     

A pharmacoeconomic evaluation of statins in the treatment of hypercholesterolaemia in the primary care setting in Spain

BACKGROUND: Cardiovascular disease is one of the leading causes of death and it has been shown that primary prevention with the HMG-CoA reductase inhibitor (statin) lipid-lowering drugs can reduce cardiovascular events. Acquisition costs vary between statins and this may be an important consideration in the overall cost effectiveness (CE) of different options. OBJECTIVE: To perform a CE study of the main statins used in Spain for primary prevention of cardiovascular disease in patients with high cholesterol levels [corrected] STUDY DESIGN: The CE analysis was based on an open-label, prospective, naturalistic, randomised intervention study under usual care conditions in primary care settings in patients with high cholesterol levels (total cholesterol [TC] >240 mg/dL, low-density lipoprotein cholesterol [LDL-C] >160 mg/dL) and one or more cardiovascular risk factors. The analysis was conducted from the perspective of the Spanish National Health System; the year of costing was 2001. PATIENTS: A total of 161 patients (49.7% males), mean age 65 +/- 10.3 years, without evidence of cardiovascular disease were included in the study. Of those, 82.1% were hypertensive, 37.1% had diabetes mellitus and 17.9% were smokers. INTERVENTIONS: Forty-eight patients received oral atorvastatin 10 mg/day, 32 received fluvastatin 40 mg/day, 44 received simvastatin 20 mg/day and 37 patients received pravastatin 20 mg/day for 6 months. MAIN MEASUREMENTS AND RESULTS: After 6 months, the therapeutic goals of LDL-C control, according to the recommendations of the Spanish Society of Arteriosclerosis--Consensus-2000, were reached in 62.5%, 43.8%, 45.5% and 40.5% of patients treated with atorvastatin, fluvastatin, simvastatin and pravastatin, respectively. The average CE ratio, expressed as the cost in euros (euro) per patient achieving the therapeutic goals, was euros 424.3 for atorvastatin, euros 503.5 for fluvastatin, euros 527.0 for simvastatin and euros 683.4 for pravastatin. The incremental CE ratios for atorvastatin versus fluvastatin and simvastatin were euros 238.9 and euros 149.5, respectively, per additional patient reaching therapeutic goals. Atorvastatin, fluvastatin and simvastatin all dominated pravastatin. CONCLUSIONS: All the statins studied have been shown to be effective for reducing both TC and LDL-C levels. In this study, atorvastatin was the most efficient drug, with the best CE ratio (cost per patient reaching therapeutic goals). Atorvastatin was more effective and less costly than pravastatin, and when compared with fluvastatin or simvastatin the additional cost per additional patient achieving therapeutic goals was 相似文献