他汀类药物的不良反应分析

目的对他汀类药物的不良反应进行分析,为临床合理用药提供依据。方法对重庆三峡中心医院2010年3月至2012年3月住院服用他汀类药物出现不良反应的85例患者的临床资料进行分析,对不良反应发生时间、他汀类药物分布、不良反应表现等进行统计。结果85例患者中60周岁以上患者有72例,占84．7％;74例患者的不良反应于服用他汀类药物1个月内发生,占87．1％;单独用药25例,联合用药60例;他汀类药物用药中以辛伐他汀为主,共55例,占64．7％;不良反应表现主要包括肌肉毒性54例、肝。肾毒性23例、胃肠道反应17例和神经系统症状15例。结论他汀类药物会产生一定的不良反应,且以肌肉毒性为主,对他汀类药物的使用需慎重,密切关注病情,及时采取应对措施。     

他汀类药物能否减少谵妄发生的Meta分析

目的 评估他汀类药物的多效性能否减少谵妄的发生。方法 检索2000年1月至2016年6月PubMed、万方数据库、Cochrane library、EMBase、维普中文数据库、中国期刊全文数据库收录的关于他汀类药物使用能否减少谵妄发生的随机对照试验文献,以“谵妄,ICU谵妄,他汀,辛伐他汀,阿托伐他汀,西立伐他汀,氟伐他汀,洛伐他汀,美伐他汀,普伐他汀,罗素伐他汀,HMG-CoA还原酶阻滞剂”等为检索词检索,使用Jadad量表对纳入的文献进行严格的质量评价,主要评估指标为使用他汀类药物是否有效,次要评估指标包括住院时间,机械通气的例数,最后用RevMan5.2统计软件进行系统分析。结果 共纳入7项研究,290 274例患者。其中,显示服用他汀类药物不能减少谵妄的发生率（OR：1.01;95% CI：0.81~1.26）,也不能缩短住院时间（WMD：1.93;95% CI：-5.62~9.47）。但是,他汀类药物能够减少危重患者机械通气的发生率（OR：0.65;95% CI：0.47~0.90）。结论 使用他汀类不能减少谵妄的发生。     

Early vascular benefits of statin therapy

SUMMARY

Large-scale trials established that statin administration in hypercholesterolaemic individuals and patients with coronary heart disease (CHD) significantly reduces the risk of vascular events and death. This benefit was primarily attributed to their actions on lipids. This review focuses on the benefits (clinical and experimental) of statins observed soon (approximately 12 weeks) after their administration.

Statins rapidly increase nitric oxide production and improve endothelial function (e.g. increased flow-mediated dilatation). Similarly, antioxidant properties decrease the susceptibility of low density lipoprotein cholesterol to oxidation. Statins inhibit the migration of macrophages and smooth muscle cell proliferation leading to an antiproliferative effect and the stabilisation of atherosclerotic plaques. Anti-inflammatory effects include a reduction in serum C-reactive protein levels, inflammatory and proinflammatory cytokines (e.g. IL-6, IL-8), adhesion molecules (e.g. ICAM-1, VCAM-1) and other acute phase proteins. Statins influence the haemostatic system. They reduce tissue factor expression and platelet activity, whereas fibrinolysis can be enhanced. Statins improve microalbuminuria, renal function, hypertension and arterial wall stiffness. A significant reduction of the carotid intima media thickness (IMT) was also reported early after statin treatment.

These early effects of statins probably contribute to the significant reduction in vascular events seen in some 'short-term' studies. There is a need to further elucidate the rapid and non-lipid-lowering properties of statins.     

Exploring the association between stroke and acute myocardial infarction and statins adherence following a medicines co-payment increase

ObjectivesPatient contributions (co-payments) for one months' supply of a publicly-subsidised medicine in Australia were increased by 21% in January 2005 (US$2.73-$3.31 for social security recipients and $17.05-$20.58 for others). This study investigates the relationship between patients’ use of statin medication and hospitalisation for acute coronary syndrome and stroke, following this large increase in co-payments.MethodsWe designed a retrospective cohort study of all patients in Western Australia who were dispensed statin medication between 2004 and 05. Data for the cohort was obtained from State and Federal linked databases. We divided the cohort into those who discontinued, reduced or continued statin therapy in the first six months after the co-payment increase. The primary outcome was two-year hospitalisation for acute coronary syndrome or stroke-related event. Analysis was conducted using Fine and Gray competing risk methods, with death as the competing risk.ResultsThere were 207,066 patients using statins prior to the co-payment increase. Following the increase, 12.5% of patients reduced their use of statin medication, 3.3% of patients discontinued therapy, and 84.2% continued therapy. There were 4343 acute coronary syndrome and stroke-related hospitalisations in the two-year follow-up period. Multivariate analysis demonstrated that discontinuing statins increased the risk of hospitalisation for acute coronary syndrome or stroke-related events by 18% (95%CI = 0.1%–40%) compared to continuing therapy. Subgroup analysis showed that men aged <70 years were at increased risk of 54–63% after discontinuing statins compared to those continuing, but that women and older men were not.ConclusionDiscontinuing statin medication after a large increase patient cost contribution was associated with higher rates of acute coronary syndrome and stroke-related hospitalisation in men under 70 years. The findings highlight the importance of continued adherence to prescribed statin medication, and that discontinuing therapy for non-clinical reasons (such as cost) can possibly have negative consequences particularly for younger men.     

Estimating the economic value of British Columbia's domestic cannabis market: Implications for provincial cannabis policy

BackgroundBritish Columbia (BC), Canada, is home to a large illegal cannabis industry that is known to contribute to substantial organized crime concerns. Although debates have emerged regarding the potential benefits of a legally regulated market to address a range of drug policy-related social problems, the value of the local (i.e., domestically consumed) cannabis market has not been characterized.MethodsMonte Carlo simulation methods were used to generate a median value and 95% credibility interval for retail expenditure estimates of the domestic cannabis market in BC. Model parameter estimates were obtained for the number of cannabis users, the frequency of cannabis use, the quantity of cannabis used, and the price of cannabis from government surveillance data and studies of BC cannabis users.ResultsThe median annual estimated retail expenditure on cannabis by British Columbians was $407 million (95% Credibility Interval [CI]: $169–948 million). Daily users accounted for the bulk of the cannabis revenue, with a median estimated expenditure of approximately $357 million (95% CI: $149–845 million), followed by weekly users ($44 million, 95% CI: $18–90 million), and monthly users ($6 million, 95% CI: $3–12 million). When under-reporting of cannabis use was adjusted for, the estimated retail expenditure ranged from $443 million (95% CI: $185–1 billion) to $564 million (95% CI: $236–1.3 billion).ConclusionBased on local consumption patterns, conservative estimates suggest that BC's domestic illegal cannabis trade is worth hundreds of millions of dollars annually. Given the value of this market and the failure and harms of law enforcement efforts to control the cannabis market, policymakers should consider regulatory alternatives.     

Statins and the potential for higher diabetes mellitus risk

ABSTRACT

Introduction: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for cardiovascular disease (CVD) prevention. Long-term use of statins has been linked to the development of diabetes mellitus (DM) which increases CVD risk.

Areas covered: We discussed the reported incidence of DM in statin users, various possible mechanisms responsible for the development of DM and the clinical implications of this association on CVD risk. Relevant supporting literature was identified using MEDLINE/EMBASE search.

Expert opinion: Data from available RCTs and observational studies suggest a 10–45% higher risk of new-onset DM with statin use compared to nonusers. Several cellular, molecular, and genetic mechanisms, and lifestyle changes have been studied and discussed as potential underlying mechanisms responsible for this elevated DM risk with statin therapy. The mode of the diabetogenic action of statins is still unclear and an interplay of pancreatic and peripheral effects in the pathogenesis of DM is a possibility. Despite these observations, the CVD preventative benefit of statin treatment outweighs the CVD risk associated with of development of new DM. There is a need for further research to identify the exact mechanisms involved so as to specifically target causative factors and individualize treatment.     

他汀类药物在急性冠脉综合征住院患者应用现状调查

目的 调查他汀类药物在急性冠脉综合征患者住院期间的应用情况。方法 调查2012年7月—2013年5月所有ACS患者452例,调查其他汀类药物的应用情况。结果 452例患者中有425例（94％）应用他汀类药物,最常用的他汀是阿托伐他汀,平均剂量16mg／d。15例（3．5％）患者应用强化剂量的他汀,96．5％患者接受标准剂量的他汀。27例没有应用他汀类药物患者中,7例有他汀禁忌症,20例没有禁忌症。住院期间应用他汀类药物与入院时LDL—C水平无关。结论 在冠脉综合征住院患者中,接受他汀类药物的比例较高,但剂量不足,与指南推荐存在较大差距,需要加强对医生的教育。     

Differences between statins on clinical endpoints: a population-based cohort study

ABSTRACT

Objective: Many studies have shown differences between statins based on surrogate endpoints, but few have studied differences in reaching clinical endpoints.

This study compares the risk of cardiovascular and cerebrovascular events between atorvastatin users and other statin users in daily general practice.

Research design and methods: A cohort study was performed in the Integrated Primary Care Information project database, a longitudinal general practice research database with electronic patient records of more than 500?000 individuals in the Netherlands. All new statin users in the period 1st September 1999 to 31st December 2002 were included. Multivariate Cox-regression analysis was used to compare the occurrence of the primary endpoint between atorvastatin users and other statin users.

Main outcome measures: The primary endpoint was the composite outcome of fatal or non-fatal myocardial infarction, admission for unstable angina pectoris, fatal or non-fatal cerebrovascular accidents, or transient ischaemic events.

Results: 3499 new statin users were identified, including 797 patients with a history of cardiovascular disease. 1341 persons started with simvastatin (38.3%), 1154 with atorvastatin (33.0%), 811 with pravastatin (23.2%) and 193 with other statins (5.5%). The median follow-up was 1.9 years. Two hundred and thirty three patients (6.7%) experienced a primary endpoint. Atorvastatin users had a significantly lower risk of cardiovascular and cerebrovascular events than users of other statins (relative risk [RR]: 0.70, 95% confidence interval [CI]: 0.55–0.96). The relative risks of atorvastatin users compared to simvastatin and pravastatin users individually were 0.70 (95% CI: 0.48–1.02) and 0.78 (95% CI: 0.52–1.16), respectively. The protective effect of atorvastatin was more pronounced in persons without a history of cardiovascular or cerebrovascular events.

Conclusion: Atorvastatin showed a more favourable effect on fatal and non-fatal cardiovascular and cerebrovascular events in the general population than other statins.     

A systematic review to assess adherence and persistence with statins

Objective: To identify and assess studies published over a 10 year period up to February 2016 which measure adherence or persistence with statins, to summarize their methods, strengths and weaknesses and to summarize evidence linking statin adherence/persistence with risk of cardiovascular events.

Methods: Electronic databases and abstracts from four major cardiovascular disease conferences were searched from January 2005 to February 2016. The study selection process was performed by two reviewers working independently. Studies were included if they reported data regarding patient adherence or persistence with statins in adults with primary hypercholesterolemia, using any type of study design or length of follow-up. One reviewer extracted the study data and assessed study quality, which was checked by a second reviewer independently. Given the heterogeneity between the included studies a narrative critique and summary is presented.

Results: We report on 84 real world studies which aimed to assess adherence or persistence with statins. The majority of studies concluded that good adherence/persistence was associated with reduction in cardiovascular events and mortality. In two studies high intensity statin regimens were associated with poorer patient adherence when compared to low intensity statins. Adherence and persistence with statin therapy also has an impact on hospitalization costs and other cardiovascular disease (CVD) related costs.

Conclusions: Adherence and persistence are associated with a reduction in CVD events and mortality. There was limited evidence to suggest that high intensity statin regimens are associated with poorer treatment adherence when compared to lower intensity regimens. Hence, more robust studies are required to establish this association. As recommended by the 2013 ACC/AHA, 2016 ESC and several other clinical guidelines, clinicians and pharmacy managers should regularly monitor statin therapy adherence.     

The potential role of statins in preeclampsia and dyslipidemia during gestation: a narrative review

Introduction: Statins have several pleiotropic effects that have the potential to be beneficial during pregnancy. This study evaluates the available evidence for the teratogenicity of statins, and their utility in treating preeclampsia and dyslipidemia in pregnancy, as good alternatives in these domains are currently lacking.

Areas covered: The possible teratogenicity of statins is a primary focus of this paper. We also evaluated for some possible non-teratogenic effects, such as changes in birth weight and rates of spontaneous abortion, among mothers exposed to statins during pregnancy. Regarding potential uses, this study mainly discusses statin utility in preventing and treating preeclampsia and treating dyslipidemia in pregnancy. Within the latter, we explore the relationship between dyslipidemia and preeclampsia, the potential consequences of delaying statin therapy where indicated, and the impact of supra-physiological levels of cholesterol in utero on offspring. The literature search was conducted using Embase, Web of Science, PubMed, and Scopus.

Expert opinion: Based on current evidence, statins are likely not teratogenic. Limited, but promising evidence exists for their efficacy in treating and preventing preeclampsia. In utero exposure to high cholesterol may negatively impact offspring, and should be thoroughly investigated.     

Medication non-adherence and uncertainty: Information-seeking and processing in the Danish LIFESTAT survey

Background

Statins are widely prescribed to lower cardiovascular morbidity and mortality. However, statin non-adherence is very high.

Comparative effectiveness of rosuvastatin versus other statin therapies in patients at increased risk of failure to achieve low-density lipoprotein goals

ABSTRACT

Objectives: Statins are increasingly used in the treatment of hypercholesterolemia. Research has shown difficulty in attaining LDL?C goals in routine clinical practice, especially in patients at high risk for coronary events. This study identified risk factors associated with failure to attain LDL?C goals in routine clinical practice and examined the effectiveness of rosuvastatin compared to other statins in patients presenting with these risk factors.

Methods: This retrospective observational study used administrative claims data on patients receiving statins. After stratifying patients into baseline National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) risk categories, logistic regression allowed identification of factors predicting failure to attain LDL?C goal. Separate analyses compared failure rates between rosuvastatin and other statins in patients at an increased risk of goal attainment failure.

Results: Of the 4661 patients identified, 50% and 14% had baseline NCEP ATP III high and moderate risk status, respectively. Risk factors associated with goal attainment failure were percentage change required to achieve goal ≥ 30%, NCEP high risk status, percentage change required 15–29%, and NCEP moderate risk status. Patients at an increased risk of failure exhibited significantly higher failure rates in all other statin groups compared to rosuvastatin.

Conclusions: This study demonstrates that patients requiring ≥ 15% change in LDL?C or NCEP high or moderate risk patients are at a higher risk of goal attainment failure. Rosuvastatin is more effective compared to other statins in patients with these risk factors and given variations in clinical profiles of branded and generic statins, these results may aid in identifying patients most likely to benefit from rosuvastatin compared to other statin therapies. Validating the results of this study in other patient populations would help increase the generalizability of study findings.     

Preoperative statins and infectious complications following cardiac surgery

ABSTRACT

Purpose: Recent observational studies have suggested that statins can decrease the incidence and severity of various infections including pneumonia and bacteremia. However, the effect of statins on post-cardiac surgery infection has not been adequately evaluated. Therefore we sought to determine whether preoperative statin use resulted in a reduction in infection following cardiac surgery.

Methods: This was a cohort evaluation of all consecutive patients who underwent coronary artery bypass graft (CABG) and/or valve surgery at our institution between January 1, 2004 and August 31, 2006. Our primary outcome measure was the occurrence of at least one of the following postoperative infectious complications (pneumonia, bacteremia, sternal wound, leg vein harvest site infection, urinary tract infection, or tracheotomy site infection). We used multivariable logistic regression to control for potential confounding and to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs).

Results: A total of 1934 patients were included in this evaluation of which 1248 received a statin preoperatively and 686 did not. Our study population was 66.3 ± 11.6 years of age, 71.3% male; 37.2% underwent complex surgery, 3.6% were morbidly obese, and 32.0% were diabetic (each being previously identified as an independent predictor of infection following cardiac surgery). Patients receiving a statin preoperatively and not receiving a statin preoperatively varied in respect to a number of important pre- and peri- operative character­istics. Patients receiving preoperative statin therapy were more likely to have had a history of diabetes, chronic obstructive pulmonary disease or high cholesterol and to be smokers, but less likely to be undergoing urgent/emergent surgery or surgery utilizing a cardiopul­monary bypass pump (?p < 0.05 for all comparisons). In total, 151 (7.8%) patients developed an infectious complication. Upon multivariable logistic regression, preoperative statin use was associated with a significant reduction in the development of infection (AOR; 0.67 (95% CI 0.46–0.99), p = 0.04). The use of a statin was not associated with a statistically significant reduction in any individual infection on its own (?p > 0.08 for all).

Limitations: Patients were not randomized to receive statins or not. We did not have adequate power to evaluate individual infections.

Conclusions: Preoperative statin use is associated with a reduction in patients’ odds of developing a postoperative infection following cardiac surgery.     

Statins – Are they anticonvulsant?

Statins are the most popular and effective lipid-lowering medications beneficial in hypercholesterolemias and prevention of cardiovascular diseases. Growing evidence supports theory that statins exhibit neuroprotective action in acute stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis or epilepsy. Hereby, we present available experimental data regarding action of this group of drugs on seizure activity and neuronal cell death. The most commonly examined statins, such as atorvastatin and simvastatin, display anticonvulsant action with only inconsiderable exceptions. However, the mechanism of this effect remains unexplained. Simvastatin, as a lipophilic statin, which can pass blood–brain barrier easily, was recommended as the best candidate for an anticonvulsant agent. Nevertheless, it is still indistinct, whether the protective activity of statins depends on cholesterol lowering properties or its pleiotropic characteristics. One of the most interesting of 3-hydroxy-3-methylglutaryl-coenzyme A inhibitor's actions involves influence on nitric oxide metabolism.     

Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin

ABSTRACT

Background: Recent guidelines underline the need for high-risk patients to reach strict low density lipoprotein cholesterol (LDL?C) targets (1.8–2.6?mmol/L; 70–100?mg/dL), and specifically mention the possible use of combination therapy (e.g. statin + ezetimibe) to achieve these goals.

Methods: A retrospective case-note audit was carried out to assess the response to administering ezetimibe in patients unable to tolerate statins (Group 1), or high dose of statins (Group 2) and patients who cannot achieve the LDL?C target (2.6?mmol/L; 100?mg/dL) despite taking a statin (Group 3).

Results: Ezetimibe lowered LDL?C levels by 20–29% across the 3 patient groups after 2–3 months of treatment. High density lipoprotein cholesterol (HDL?C) levels tended to remain unchanged, although there was a consistent trend for a fall if baseline values were ‘high’. However, the LDL-C/HDL-C ratio changed significantly and favourably in all groups. The fall in fasting triglyceride levels in all groups was greater (reaching 19–25%) when baseline levels were ≥ 1.5 or 1.7?mmol/L (136–150?mg/dL). There were no marked abnormalities in liver function tests or creatine kinase activity. In Group 3 there was a significant trend for a fall in serum creatinine levels across the tertiles of baseline creatinine values.

Limitations of the present study include the small sample size (especially in Groups 1 and 2), its short-term duration and the absence of event-based end-points. Therefore, the results are hypothesis-generating rather than conclusive.

Conclusions: When used alone or added to a statin, ezetimibe favourably altered the LDL?C/HDL?C ratio and lowered triglyceride levels. Ezetimibe was well tolerated in patients with statin intolerance and was associated with a 26% fall in LDL?C. An additional action may be some degree of improved renal function. Further studies are needed to confirm these findings.