Efficacy of atorvastatin after LDL-cholesterol-based dose selection in high risk dyslipidaemic patients: results of the target dose study

ABSTRACT

Background: Hypercholesterolaemia is one of the major risk factors for the development of coronary heart disease (CHD). European guidelines emphasize the importance of reducing low-density lipoprotein cholesterol (LDL?C) levels below 115?mg/dL (3.0?mmol/L) in patients with high CHD risk.

Objective: The present study evaluates whether selection of the atorvastatin starting dose based on baseline LDL?C levels and previous statin treatment status would result in an achievement of LDL?C targets without the need for up-titration.

Methods: A multicentre, prospective, open-label study conducted in Belgium. Patients were at high risk defined as either a history of CHD, another atherosclerotic disease, diabetes mellitus Type 2 or an estimated 10?year CHD risk > 20%. The primary endpoint was the proportion of patients achieving the LDL?C goal after 12 weeks of treatment.

Results: Overall, 96.4% of the 195 statin-naïve patients reached the LDL?C target after 12 weeks of treatment. The majority of the patients (95.4%) already reached LDL?C control at Week 6. Mean (SD) LDL?C levels decreased from 159 (25)?mg/dL[(4.1 (0.6)?mmol/L] to 86 (14)?mg/dL [2.2 (0.4)?mmol/L] after 12 weeks of treatment. Only 4.6% of the patients needed an up-titration at Week 6.

Conclusions: Taken together, the results demonstrate that LDL?C based dose selection of atorvastatin is highly efficacious for rapid achievement of target LDL?C levels with a low need for up-titration. Application of this flexible first dosing strategy in general practice will, based on available evidence, increase adherence to atorvastatin treatment in patients with high CHD risk.     

大剂量阿托伐他汀预防脑血管介入诊疗术后造影剂肾病的临床研究

目的研究大剂量阿托伐他汀预防脑血管介入术后造影剂肾病(CIN)的效果及其作用机制。方法选择2014年7-12月我院收治的95例行脑血管介入术诊疗的脑血管病患者为研究对象,随机分为对照组(46例)和观察组(49例)。术前3 d及术后,对照组口服阿托伐他汀20 mg/d,观察组于术前夜间予阿托伐他汀80 mg顿服,术后予阿托伐他汀40 mg/d。分别于术前24 h和术后24、72 h检测血肌酐(Scr)、肌酐清除率(Ccr)、血清尿素(BUN)、β2-微球蛋白(β2-M G)、胱抑素-C(CYS-C)、超敏C反应蛋白(hs-CRP)水平;以及术前24 h和术后72 h的血脂和肝功能水平,并进行对比分析。同时比较CIN和脑血管不良事件的发生率。结果两组患者术前24 h的Scr、Ccr、BUN、β2-M G、CYS-C、hs-CRP水平比较,差异均无统计学意义(P>0.05)。对照组术后各时间点Scr、β2-M G、CYS-C、hs-CRP均较术前升高,Ccr较术前降低,差异均有统计学意义(P<0.05)。观察组术后除CYS-C水平较术前升高(P<0.05)外,其余各项指标水平与术前比较,差异均无统计学意义(P>0.05)。两组患者之间术后各时间点各项指标的水平比较,观察组均优于对照组,差异有统计学意义(P<0.05)。两组患者术前术后肝功能和血脂水平组间及组内比较,差异均无统计学意义,无不良脑血管事件发生。结论脑血管介入术前给予大剂量阿托伐他汀可减轻肾损害,机制与其抑制炎症因子有关。     

高龄急性心肌梗死患者PCI围术期服用高剂量阿托伐他汀的疗效及安全性研究

目的：探讨高龄急性心肌梗死患者急诊经皮冠状动脉介入治疗（Percutaneous coronary intervention,PCI）围术期服用高剂量阿托伐他汀的疗效及安全性。方法：将急诊PCI手术治疗的高龄急性心肌梗死患者120例,随机分为实验组和对照组,每组60例,除接受常规药物治疗外,实验组：术前半小时口服负荷量阿托伐他汀80mg,术后d1开始口服40mg,每晚1次,持续3个月;对照组：术前半小时口服阿托伐他汀20mg,术后d1开始口服20m,每晚1次,持续3个月。比较两组术前半小时血清中肌钙蛋白（cTnI）、超敏C反应蛋白（hs-CRP）、胱抑素C、肌酐水平及术后24h cTnI、hs-CRP和术后48h胱抑素C、肌酐的水平;并比较术后3个月两组的LDL、肌酐、胱抑素C、肝功能,和主要不良事件（心源性死亡、急性心肌梗死、心力衰竭、心绞痛发作、肝损害及股骨肌溶解等）的发生情况。结果：实验组PCI术后24h cTnI、hs-CRP水平及术后48h胱抑素C、血清肌酐的水平均较对照组显著降低（P<0．05）,实验组术后3月LDL较对照组显著下降（P<0．05）,急性心肌梗死、心绞痛发生率显著低于对照组（P<0．05）。结论：高龄急性心肌梗死患者PCI围术期高剂量阿托伐他汀治疗疗效好且安全,值得临床推广。     

阿托伐他汀联合依折麦布在ACS患者PCI术后的应用效果

目的 观察阿托伐他汀联合依折麦布在急性冠脉综合征(ACS)患者经皮冠状动脉介入治疗(PCI)术后的应用效果.方法 行PCI的ACS患者168例随机分为治疗组(88例)和对照组(80例).治疗组术后口服阿托伐他汀20 mg/d联合依折麦布10 mg/d,对照组口服阿托伐他汀20mg/d,治疗12个月.比较两组治疗前后血脂...     

Efficacy and safety of high dose fluvastatin in patients with familial hypercholesterolaemia

Summary The efficacy and safety of the HMG CoA reductase inhibitor fluvastatin have been evaluated in a double blind study in 52 patients with familial hypercholesterolaemia. A standard AHA Phase II lipid lowering diet was prescribed throughout the study. After 6 weeks of a single blind dosage stabilisation period, in which patients received fluvastatin 40 mg qPM, patients were randomly allocated to one of two double blind treatment groups: group A (n=24) received fluvastatin 20 mg b. d. for 12 weeks and fluvastatin 20 mg AM + 40 mg PM for an additional 12 weeks; Group B (n=28) received fluvastatin 40 mg qPM during the entire study. Safety and tolerability were evaluated by the analysis of biochemical and haematological parameters, and ophthalmological and physical examinations. Efficacy was analysed by the determination of plasma lipids, lipoproteins and apoproteins.Fluvastatin 40 mg/d was associated with up to a 27.4% decrease in LDL-C and a 9.6% increase in HDL-C concentrations. Increasing the dose of fluvastatin from 20 mg b. d. to 60 mg per day in Group A was associated with a 7.1% decrease in LDL-C, a 12.1% increase of HDL-C and a 12.8% decrease in the LDL-C/HDL-C ratio. In comparison with Group B (40 mg qPM) LDL-C, HDL-C and the LDL-C/HDL-C ratio in Group A (60 mg) differed by –8.9%, 6.6% and –12%, respectively. During treatment with 40 mg qPM, one patient developed an asymptomatic but notable elevation of CK to 1823 U/l (normal range 0–100 U/l) that was caused by strenuous exercise. No other notable biochemical or haematological abnormalities were recorded.It is concluded that in patients with heterozygous FH the increase of fluvastatin from 40 to 60 mg/d provided an additional significant effect on plasma LDL-C and HDL-C levels and in the LDL-C/HDL-C ratio, without producing any deleterious effect.     

高剂量阿托伐他汀预防对比剂肾损害的临床观察

目的探讨高剂量阿托伐他汀能否预防冠状动脉介入性诊断及治疗术后的急性肾损害。方法将120例行冠状动脉介入诊断与治疗患者随机分为高剂量组和低剂量组各60例。在全部采用水化治疗和给予阿托伐他汀10mg/d的基础上,高剂量组术前12～24h阿托伐他汀加量至80mg口服。观察造影前及造影后1、3、5d血清肌酐(Scr)、内生肌酐清除率(Ccr)、血β2-微球蛋白、尿N-乙酰-β-D-葡萄糖酸苷酶(NAG)/尿肌酐(Cr)、尿渗透压的改变情况。结果造影后1、3、5d,高剂量组Ccr水平高于低剂量组,血β2-微球蛋白及尿NAG/Cr水平低于低剂量组,差异均有统计学意义(P<0.05);2组造影前后Scr、尿渗透压差异无统计学意义(P>0.05)。2组CIN发生率差异无统计学意义(P>0.05)。结论血管造影前使用高剂最(80mg)的阿托伐他汀可能有助于减少对比剂肾病的发生。     

Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation

Toxicokinetic (TK) information can substantially enhance the value of the data generated from toxicity testing, and is an integral part of pharmaceutical safety assessment. It is less widely used in the chemical, agrochemical and consumer products industries, but recognition of its value is growing, as reflected by increased reference to the use of TK information in new and draft OECD test guidelines. To help promote increased consideration of the important role TK can play in chemical risk assessment, we have gathered practical examples from the peer-reviewed literature, as well as in-house industry data, that highlight opportunities for the use of TK in the selection of dose levels. Use of TK can help to ensure studies are designed to be of most relevance to assessing potential risk in humans, and avoid the use of excessively high doses that could result in unnecessary suffering in experimental animals. Greater emphasis on the potential contribution of TK in guiding study design and interpretation should be incorporated in regulatory data requirements and associated guidance.     

大剂量阿托伐他汀联合水化对老年急诊PCI术后造影剂肾病的保护作用

目的探讨阿托伐他汀(80 mg)联合水化对老年(年龄≥60岁)急诊冠状动脉介入术(PCI)术后造影剂肾病的保护作用。方法 92例患者随机分为大剂量强化治疗组、常规剂量治疗组、空白对照组,3组患者在水化治疗的基础上,大剂量强化治疗组:入院后口服阿托伐他汀80 mg,急诊PCI术后3 d内口服阿托伐他汀40 mg.d-1;常规剂量治疗组:入院后口服阿托伐他汀20 mg,急诊PCI术后3 d内口服阿托伐他汀20 mg.d-1;空白对照组:术前未给予他汀类药物。分别测定3组患者术后24,72 h的血肌酐(Scr)、尿素氮(BUN)、内生肌酐清除率(Ccr)以及造影剂肾病的发生率。结果急诊PCI术后24 h与PCI术前相比,大剂量强化治疗组BUN,Scr的增加值较常规剂量治疗组小,差异有统计学意义(P<0.05)。急诊PCI术后72 h与PCI术前相比,大剂量强化治疗组BUN,Scr的增加值以及Ccr的下降值明显低于常规剂量治疗组(P<0.05)。结论大剂量阿托伐他汀联合水化对老年急诊PCI术后造影剂肾病具有一定的保护作用。     

较大剂量阿托伐他汀钙治疗老年混合型高脂血症的临床疗效及其安全性

目的探讨较大剂量阿托伐他汀钙治疗老年混合型高脂血症的临床疗效及其安全性。方法选取吉安市中医院2017年10月-2019年4月收治的老年混合型高脂血症患者92例,采用分层随机法分为对照组和观察组,各46例。对照组给予常规剂量阿托伐他汀钙,观察组给予较大剂量阿托伐他汀钙,两组均治疗3个月。比较两组治疗前后高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、三酰甘油(TG),并观察两组不良反应发生情况。结果治疗前两组HDL-C、LDL-C、TC、TG比较,差异无统计学意义(P>0.05);治疗后观察组HDL-C高于对照组,LDL-C、TC、TG低于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论较大剂量阿托伐他汀钙治疗老年混合型高脂血症的临床疗效确切,可有效改善患者血脂指标,且安全性较高。     

大剂量阿托伐他汀对经皮冠状动脉介入治疗患者术后造影剂肾病的影响

目的探讨大剂量阿托伐他汀对经皮冠状动脉介入治疗（PCI）术后肾功能的影响。方法 68例冠状动脉造影患者随机分为80 mg组（36例）、20 mg组（32例）。各组患者于术前第4天起每晚顿服阿托伐他汀,并于术前及术后24、48 h测定肾功能指标（Scr、BUN）和CIN发生率。结果两组术后24 h的Scr均高于术前（P〈0.05）;80 mg组术后24 h的Scr低于20 mg组（P〈0.05）。20 mg组、80 mg组的CIN发生率分别为31.3%（10/32）、11.1%（4/36）,差异有统计学意义（P〈0.05）。结论术前大剂量阿托伐他汀可以改善PCI患者的肾功能,降低CIN发生率,充分保护肾功能。     

Nortriptyline therapy in elderly patients: Dosage prediction after single dose pharmacokinetic study

Summary Sixteen depressed elderly patients in hospital (mean age 81 years) received a single oral dose of nortriptyline prior to commencing treatment with this drug. Plasma nortriptyline measurements after the single dose were used to calculate the plasma drug clearance and to predict the daily dose required for each patient to achieve a steady-state concentration within the suggested therapeutic range of 50–150 µg·l^–1. Using these dosage regimes, the mean observed steady-state concentration showed a significant correlation with the predicted values (r=0.71, p<0.002). All patients had steady-state concentrations within or very close to this suggested range (mean 106, range 38–157 µg·l^–1). Use of the prediction test can prevent the development of toxic plasma concentrations and enhance the possibility of therapeutic success. Our findings suggest that a safe starting dose of nortriptyline for the elderly is 30 mg per day.     

急性脑梗死应用阿托伐他汀联合甘露醇治疗的效果分析

目的探讨阿托伐他汀联合甘露醇治疗急性脑梗死的临床效果。方法108例急性脑梗死患者,采用随机数字表法分为对照组和研究组,各54例。对照组应用甘露醇及常规对症治疗,研究组在对照组基础上联合阿托伐他汀治疗。对比两组治疗前后超敏C反应蛋白(hs-CRP)、基质金属蛋白酶9(MMP-9)、D-二聚体、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平及治疗效果、不良反应发生情况。结果研究组的治疗总有效率92.6%高于对照组的77.8%,差异具有统计学意义(P<0.05)。治疗前,两组TG、TC、LDL-C、HDL-C水平对比差异无统计学意义(P>0.05);治疗后,研究组的TG(1.82±0.38)mmol/L、TC(4.03±0.66)mmol/L、LDL-C(2.05±0.39)mmol/L均低于对照组的(2.19±0.47)、(6.01±0.71)、(2.44±0.41)mmol/L,HDL-C(1.48±0.36)mmol/L高于对照组的(1.33±0.37)mmol/L,差异具有统计学意义(P<0.05)。治疗前,两组hs-CRP、MMP-9、D-二聚体水平对比,差异无统计学意义(P>0.05);治疗后,研究组hs-CRP、MMP-9、D-二聚体水平低对照组,差异具有统计学意义(P<0.05)。两组不良反应发生率对比差异无统计学意义(P>0.05)。结论对急性脑梗死应用阿托伐他汀联合甘露醇治疗效果理想,能够更好的降低血脂及炎性因子水平,且不会增加不良反应的发生,用药安全性高,值得临床进一步推广应用。     

瑞舒伐他汀与阿托伐他汀治疗老年高胆固醇血症的疗效和安全性比较

目的比较瑞舒伐他汀10 mg·d~(-1)与阿托伐他汀20 mg·d~(-1)治疗老年高胆固醇血症病人的疗效和安全性。方法采用单盲随机对照的前瞻性研究。经4 wk调脂药物洗脱的老年病人67例,空腹血脂符合低密度脂蛋白-胆固醇(LDL-C)≥4.14 mmol·L~(-1)且≤6.50 mmol·L~(-1)、三酰甘油(TG)<4.52 mmol·L~(-1)入组标准,随机分为瑞舒伐他汀组(n=33,瑞舒伐他汀10 mg·d~(-1))和阿托伐他汀组(n=34,阿托伐他汀20 mg·d~(-1)),疗程4 wk,观察2药的疗效和安全性。结果治疗4 wk后,瑞舒伐他汀组病人血清LDL-C显著降低[(3.4±s0.9)mmol·L~(-1) vs(2.8±0.8)mmol·L~(-1),P<0.05],总胆固醇(TC)亦显著降低[(5.5±1.1)mmol·L~(-1)vs(4.8±0.9)mmol·L~(-1),P<0.051,HDL-C和TG无明显改变(P>0.05);阿托伐他汀组病人血清LDL-C水平也显著降低,[(3.3±1.2)mmol·L~(-1) vs(2.4±0.7)mmol·L~(-1),P<0.05],TC降低明显[(5.2±1.2)mmo]·L~(-1)vs(4.5±0.6)mmol·L~(-1),P<0.05],HDL-C和TG无显著改变(P>0.05)。2组间比较各指标均无显著差异(P>0.05)。研究期间未发现与药物有关的严重不良事件。结论瑞舒伐他汀和阿托伐他汀均为安全快速降低老年人群LDL-C的候选药物。     

大剂量地塞米松治疗成人原发性免疫性血小板减少症的效果

目的 观察大剂量地塞米松(Dex)冲击治疗原发性免疫性血小板减少症(PITP)的近期疗效.方法 人选PITP患者81例.其中的初治PITP患者69例分为两组:A组,36例,用Dex40 mg/d静滴,连用4d为一疗程;B组33例,以泼尼松1 mg·kg1·d1,口服,连用4周作为对照.A组Dex一个疗程后,治疗有效的32例分为两个亚组:A1组,17例,再以小剂量泼尼松维持治疗;A2组,15例,不用泼尼松治疗.12例PITP复治者为脾脏切除组(C组),术前给予Dex 40 mg/d静滴,连用4d.结果 治疗后第5天,A组总有效率达88.9％,血小板数(中位数)显著高于B组(79×109/L vs.47×109/L) (P＜0.01).治疗后第14天,A1组血小板数上升患者的比例明显高于A2组(58.8％ vs.33.3％)(P＜0.05).C组患者均顺利完成腹腔镜脾脏切除术.结论 对PITP患者,大剂量Dex短期冲击治疗效果良好.     

阿托伐他汀和瑞舒伐他汀对急性心肌梗死患者的有效性及安全性评价

目的评价急性心肌梗死患者应用阿托伐他汀和瑞舒伐他汀治疗效果及安全性。方法选取本院自2017年1月～2018年4月收治的100例急性心肌梗死患者展开研究,根据计算机分组法将其分为对照组(阿托伐他汀治疗)与治疗组(瑞舒伐他汀治疗),两组均50例患者,分析两组血脂水平、心功能、不良反应发生率、心绞痛发生率。结果治疗组血脂水平、心功能优于对照组,差异有统计学意义(P 0.05);与对照组相比,治疗组心绞痛发生率较低,差异有统计学意义(P 0.05)。两组患者均部分出现轻微的胃肠道反应、呕吐等不良反应,护胃对症处理后,所有不良反应全部消失,差异无统计学意义(P 0.05)。结论阿托伐他汀和瑞舒伐他汀应用于急性心肌梗死患者临床治疗中,均具有一定的治疗效果,但后者在改善血脂水平、心功能中效果明显优于前者。且所产生的不良反应经正确处理后,均可有效缓解,用药安全性较高,值得临床推广应用。