脑血栓患者阿司匹林联合他汀类药物对颈动脉斑块的影响分析

目的探究脑血栓患者阿司匹林联合他汀类药物对颈动脉斑块的影响。方法资料随机选自2011年12月—2013年12月在本院诊治的脑血栓患者84例,按照随机数字表方法分成两组,每组42例,予以阿司匹林作对照组,予以阿司匹林联合他汀类药物作研究组,分析两组临床疗效、神经功能评分和颈动脉斑块的面积情况。结果研究组有效率95.24%,比对照组78.57%高,比较具统计学上的意义（P〈0.05）;且两组神经功能的缺损评分与颈动脉的斑块面积,均比治疗前低,比较差异明显具统计学上的意义（P〈0.05）;同时研究组神经功能的缺损评分与颈动脉的斑块面积,均比对照组低,比较差异明显具统计学上的意义（P〈0.05）。结论对脑血栓予阿司匹林联合他汀类药物,疗效显著,且颈动脉斑块改善明显,具有一定临床应用和研究价值。     

Simvastatin dose and risk of rhabdomyolysis: Nested case–control study based on national health and drug dispensing data

Background

Two randomised controlled trials have found a higher risk of rhabdomyolysis in users of 80 mg versus 20 mg simvastatin, but there is very limited information about the risk associated with other doses. We undertook a nested case–control study, using routinely collected national health and drug dispensing data, to estimate the relative and absolute risks of rhabdomyolysis resulting in hospital admission or death according to simvastatin dose.

Methods and results

The underlying study cohort comprised all patients (n = 313,552) who initiated a new episode of simvastatin use in New Zealand between 1 May 2005 and 31 December 2009. Cases (n = 29) were patients with a diagnosis of rhabdomyolysis after cohort entry, confirmed by hospital discharge letter or death records. Ten controls, matched by year of birth and sex, were randomly selected from the study cohort using risk set sampling. Current users of 40 mg simvastatin daily were about five times as likely to develop rhabdomyolysis as those taking 20 mg; the adjusted odds ratio was 5.3 (95% CI 1.9–15.0). The absolute excess risk of rhabdomyolysis associated with the use of 40 mg versus 20 mg was about 10 per 100,000 person-years; the crude incidence rates were 11.5 (95% CI 7.1–17.5) and 2.1 (95% CI 0.7–4.8) per 100,000 person-years respectively.

Conclusions

These findings provide reassurance that the absolute risk of rhabdomyolysis in a general population of simvastatin users is very low. Nonetheless, they also raise questions about the optimal simvastatin regimen to maximise cardiovascular benefits and minimise the risk of serious muscle injury.     

Effectiveness of combined therapy with angiotensin-converting enzyme inhibitors and statins in reducing mortality in diabetic patients with critical limb ischemia: An observational study

Aims

To investigate the effect of combined treatment with angiotensin-converting enzyme inhibitors (ACE) and statins on mortality in diabetic patients with critical limb ischemia (CLI).

Methods

Prospective observational study of 553 consecutive diabetic patients admitted because of CLI followed for a mean of 2.2 years. All patients underwent peripheral revascularization and antithrombotic therapy was prescribed or continued and therapy with statin and ACE was recorded. Mortality from any cause was assessed and Kaplan–Meier analyses were performed to compare the relationship between survival and recorded variables.

Results

One hundred thirty-nine patients did not have therapy with statin or an ACE, 78 had therapy with statin without ACE, 164 had therapy with ACE without statin and 172 patients had therapy with both statin and ACE. One hundred thirty-six patients died, 45/139 with neither statin nor ACE, 40/164 with ACE only, 26/78 with statin only, and 25/172 with both statin and ACE. Multivariate analysis confirmed the independent role of age, history of stroke, renal insufficiency and dialysis. Combined treatment with ACE and statin appeared to have a protective role.

Conclusions

In patients with diabetes and CLI mortality after two years is high. Life expectancy was better in patients receiving combined therapy with ACE and statin but not with therapy with only a statin or an ACE.     

Statin therapy and risk of diabetes in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia

Objective

Controversial findings exist regarding potential influence of statin therapy on diabetic incidence. Aim of this study was to investigate the role of long duration statin treatment on diabetes mellitus (DM) incidence of Heterozygous Familial Hypercholesterolemia (hFH) and Familial Combined Hyperlipidemia (FCH) patients.

Methods

Study population consisted of 212 hFH and 147 FCH patients that visited Lipid Outpatient Department (mean follow up of 11 and 10 years respectively). Several clinical data such as history of DM, cardiovascular disease, thyroid function, metabolic syndrome, glucose levels, lipid profile and lifestyle data were obtained. In order to compare the effects of different doses of different types of statins, a “statin treatment intensity product” was used.

Results

14% of FCH and only 1% of hFH patients developed DM during follow up. Although univariate analysis showed a statistical trend (p = 0.06) in the association between new onset DM and statin treatment intensity (STI) in the FCH subgroup of patients with normal baseline glucose levels, this was no longer significant after adjusting for several confounders. Furthermore, the type of statins used did not seem to play a role in the development of DM either in hFH or FCH patients.

Conclusion

Long duration of high STI does not seem to be associated with diabetic risk in hFH patients. High STI used in the FCH population is not associated with increased risk of new onset DM compared to low STI. Further studies are required in order to clarify the potential diabetogenic effects of statins in these high risk populations.     

A systematic review of the time course of atherosclerotic plaque regression

Objective

We sought to determine the time required for lipid treatment to produce regression of atherosclerotic plaques.

Background

The cholesterol content of atherosclerotic plaques contributes to their instability, and most acute cardiac events including myocardial infarction and sudden death are produced by coronary plaque disruption. We systematically reviewed the literature on atherosclerosis regression to identify the time required for cholesterol egress, plaque regression, and possible plaque stabilization. Such information may help decide when patients with statin side effects or other reasons for statin discontinuation could consider a reduction in the intensity of treatment.

Methods

We performed a PubMed search to identify English language articles reporting atherosclerotic regression. Articles pertinent to the topic were reviewed in detail.

Results

We identified 189 articles, 50 of which provided sufficient information to establish a rate of regression and 31 of which demonstrated plaque regression with statin therapy in the carotid (n = 11), coronary (n = 16), and aortic (n = 4) vascular beds. Plaque regression occurred after an average of 19.7 months of treatment.

Conclusion

Regression of atherosclerotic plaque using statin therapy in those studies documenting regression occurred after an average time of 19.7 months. This suggests that patients should undergo approximately two years of aggressive lipid reduction before considering a reduction of statin therapy.     

Hypoxia/reoxygenation stress signals an increase in organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood–brain barrier: relevance to CNS drug delivery

Cerebral hypoxia and subsequent reoxygenation stress (H/R) is a component of several diseases. One approach that may enable neural tissue rescue after H/R is central nervous system (CNS) delivery of drugs with brain protective effects such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins). Our present in vivo data show that atorvastatin, a commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage in the brain after H/R, suggesting neuroprotective efficacy. However, atorvastatin use as a CNS therapeutic is limited by poor blood–brain barrier (BBB) penetration. Therefore, we examined regulation and functional expression of the known statin transporter organic anion transporting polypeptide 1a4 (Oatp1a4) at the BBB under H/R conditions. In rat brain microvessels, H/R (6% O₂, 60 minutes followed by 21% O₂, 10 minutes) increased Oatp1a4 expression. Brain uptake of taurocholate (i.e., Oap1a4 probe substrate) and atorvastatin were reduced by Oatp inhibitors (i.e., estrone-3-sulfate and fexofenadine), suggesting involvement of Oatp1a4 in brain drug delivery. Pharmacological inhibition of transforming growth factor-β (TGF-β)/activin receptor-like kinase 5 (ALK5) signaling with the selective inhibitor SB431542 increased Oatp1a4 functional expression, suggesting a role for TGF-β/ALK5 signaling in Oatp1a4 regulation. Taken together, our novel data show that targeting an endogenous BBB drug uptake transporter (i.e., Oatp1a4) may be a viable approach for optimizing CNS drug delivery for treatment of diseases with an H/R component.     

A users' guide to understanding therapeutic substitutions

Therapeutic substitutions are common at the level of ministries of health, clinicians, and pharmacy dispensaries. Guidance in determining whether drugs offer similar risk–benefit profiles is limited. Those making decisions on therapeutic substitutions should be aware of potential biases that make differentiating therapeutic agents difficult. Readers should consider whether the biological mechanisms and doses are similar across agents, whether the evidence is sufficiently valid across agents, and whether the safety and therapeutic effects of each drug are similar. This article uses a problem-based format to address the biological mechanism, validity, and results of a scenario in which therapeutic substitutions may be considered.     

他汀类药物对脑梗死患者血清C反应蛋白及预后的影响

目的探讨血清C反应蛋白(Creactiveprotein,CRP)及血脂水平与脑梗死病情严重性及预后的关系,进而了解他汀类药物对脑梗死患者血清CRP水平及预后的影响。方法采用随机、双盲、安慰剂对照的方法进行研究,将46例脑梗死患者分为对照组及辛伐他汀组(辛伐他汀40mg/d或阿托伐他汀20mg/d,连续用药7d)。治疗前后检测血清CRP、血脂、血清谷草转氨酶(AST)及血清肌酸激酶(CK)水平,应用美国国立卫生研究院卒中量表(NIHSS)及Barthel指数(BI)记分法对入选患者在入院时及3个月时的神经功能缺损程度进行评分。结果治疗前CRP水平与当时及3个月时病情显著相关(P<0.01,P<0.05),血脂水平则无此相关性。治疗后他汀组CRP水平下降,治疗前后的差值与对照组相比,差异有显著性(P<0.01)。各组入院时神经功能缺失程度评分与3个月后相比,差异有显著性(P<0.01),但不同组之间相比无明显差别。治疗后各组AST及CK水平无明显变化。结论脑梗死患者血清CRP水平与病情的严重性及预后相关。短期应用他汀类药物可以降低脑梗死患者血清CRP水平,安全性好,但对梗死后3个月的预后无明显改善作用。他汀类药物对脑梗死的疗效需要进一步研究。     

胆固醇代谢与阿尔茨海默病关系的研究进展

在阿尔茨海默病(AD)发病机制中,占主导地位是Aβ瀑流学说:由于淀粉样前体蛋白的代谢紊乱,产生了过量的Aβ42,后者迅速聚集形成寡聚物,启动了Aβ瀑流效应,造成了Aβ的沉积,形成老年斑.越来越多的实验表明,胆固醇在Aβ的产生和异常沉积过程具有重要调节作用,同时Aβ对胆固醇调节也有反馈作用,探讨两者的相互作用和影响有助于AD发病机制的阐明.而与胆固醇代谢密切相关的因素,如载脂蛋白E、调节胆固醇代谢的药物等也成为研究的热点.     

舒降之对颈动脉狭窄大鼠空间记忆改变的实验研究

目的观察舒降之对双侧颈总动脉重度狭窄的血管性认知障碍大鼠模型认知功能障碍的影响.方法用正常SD大鼠制作重度颈动脉狭窄模型后,分为舒降之治疗和生理盐水对照,2周后各组进行水迷宫行为学检测.结果 水迷宫行为学检测提示定位航行试验中:在实验的第2～5天,对照组大鼠逃避潜伏期显著长于治疗组(P＜0.01);空间探索试验中:治疗组的平台象限游泳的时间和总游泳时间之比(tP/tT)、平台象限距离和总距离之比(dP/dT)显著大于治疗组(P＜0.01).结论舒降之可改善血管性认知障碍大鼠的认知功能.