Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes.

AIMS: Statins provide effective secondary prevention in cardiovascular disease. However, it remains uncertain how soon statins should be started after an acute coronary syndrome (ACS). Recently published trials suggest starting before discharge. We hypothesize that statins should be initiated without delay. METHODS AND RESULTS: Data from a large cohort of 10,484 consecutive patients with an ACS were analysed. Of this cohort, 1426 first-time statin receivers and survivors of the first 24 h were compared with 6771 first-day survivors not receiving statin therapy. A propensity score for the likelihood of receiving statin therapy within 24 h was developed and used with other established risk factors in a multivariable analysis. There was a significantly reduced all-cause 7-day mortality in patients receiving early statin therapy [0.4 vs. 2.6%, unadjusted hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.08-0.37, adjusted HR 0.34, 95% CI 0.15-0.79]. Statistical significance was observed in patients presenting with STE-ACS (adjusted HR 0.17, 95% CI 0.04-0.70) and not in NSTE-ACS patients. However, no statistical evidence of heterogeneity in treatment effect was observed between these groups. CONCLUSION: These data suggest that very early statin therapy is associated with reduced mortality in patients presenting with STE-ACS; however, these findings have to be confirmed by prospective, randomized controlled trials before firm treatment recommendations can be given.     

某院住院患者他汀类药物使用情况调查与分析

目的 分析某三甲医院住院患者他汀类药物临床应用状况,为临床合理用药提供参考。方法 2013年某三甲医院应用他汀类药物的住院患者共2 561例,收集其疾病诊断、检验结果和住院期间所有用药信息,按《中国成人血脂异常预防指南》（“指南”）将研究对象进行危险分层,了解研究临床他汀类药物应用与“指南”的差距并分析可能的原因。结果 以心脑血管疾病（以心内科、神经内科计）住院的患者共1 480例（57.79%）;具有完整危险分层和血脂指标资料者1 487例（58.06%）,其中极高危162例（10.89%）,高危852例（57.30%）,中危117例（7.89%）,低危356例（23.94%）;血脂指标符合“指南”药物治疗标准的1 265例（49.39%）;低密度脂蛋白胆固醇（LDL-C）≥4.92 mmol/L的136例（10.75%）,≥4.14 mmol/L的271例（21.42%）,≥2.60 mmol/L的368例（29.09%）,≥2.07 mmol/L的490例（38.74%）。他汀类药物治疗后LDL-C达到目标值的34例（2.69%）,有疑似他汀类药物不良反应的458例（17.88%）,出现可能为他汀类药物相互作用的2 119例次。结论 该医院住院患者他汀类药物临床应用与“指南”存在着较大差距,临床医生应加强调脂知识学习,进一步规范他汀类药物的临床应用,避免过度用药。     

A comparative study of anti-inflammatory and antidyslipidemic effects of fenofibrate and statins on rheumatoid arthritis

Abstract

We prospectively compared the anti-inflammatory and antidyslipidemic effects of fenofibrate and statins in rheumatoid arthritis (RA) patients. Forty-four RA patients [male (M) = 7, female (F) = 37] with dyslipidemia were enrolled in this 6-month study and randomly allocated to the fenofibrate (2 M + 21 F = 23) or statins (5 M + 16 F = 21) group. We measured blood chemistry (serum lipid profile, sugar, urate, and γ-glutamyl transpeptidase) and blood pressure 2 h after breakfast. Visual analog scale (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and prednisolone (PSL) dosage were also recorded immediately before and after the study. Fenofibrate, but not statins, significantly decreased serum levels of total cholesterol, low-density lipoprotein–cholesterol, and triglycerides (all p < 0.05). A significant improvement in VAS was observed in both the fenofibrate group (49.1 ± 24.7 → 14.7 ± 11.2; p < 0.0001) and the statins group (47.4 ± 29.7 → 20.2 ± 16.5; p < 0.001). PSL dosage significantly decreased only in the fenofibrate group (3.58 ± 2.68 → 2.00 ± 2.22 mg/day; p < 0.01). Significant correlation was observed between ?VAS and ?CRP in the fenofibrate group (p < 0.05). Fenofibrate showed more anti-inflammatory and antidyslipidemic activity than statins in RA.     

Contribution of the WHHL rabbit,an animal model of familial hypercholesterolemia,to elucidation of the anti-atherosclerotic effects of statins

This year marks the 40th year since the discovery of a mutant rabbit showing spontaneous hyperlipidemia, which is the proband of the Watanabe heritable hyperlipidemic (WHHL) rabbit strain, an animal model of familial hypercholesterolemia, and the first statin, a general term for inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, a rate limiting enzyme in cholesterol biosynthesis. Nowadays, statins are the primary drug of choice for treating cardiovascular disease. Although several reviews have described clinical trials and in vitro studies of statins, the anti-atherosclerotic effects of statins on animal models have not been comprehensively reviewed. This review summarized the contribution of WHHL rabbits to elucidating the anti-atherosclerotic effects of statins in vivo. Studies using WHHL rabbits verified that statins suppress plaque destabilization by reducing unstable components (foam cells derived from macrophages, foam cell debris, and extracellular lipid accumulation), preventing smooth muscle cell reductions, and increasing the collagen content of plaques. In addition, the expression of matrix metalloproteinases and tissue factor are decreased in intimal macrophages by statin treatment. Lipid-lowering effects of statins alter plaque biology by reducing the proliferation and activation of macrophages, a prominent source of the molecules responsible for plaque instability and thrombogenicity. Although statins remain the standard treatment for cardiovascular disease, new therapeutics are eagerly awaited. WHHL rabbits will continue to contribute to the development of therapeutics.     

A promoter polymorphism in cholesterol 7alpha-hydroxylase interacts with apolipoprotein E genotype in the LDL-lowering response to atorvastatin

Bile-acid biosynthesis is a key determinant of intracellular cholesterol and, in turn, cholesterol synthesis rate in hepatocytes. This suggests that variation in the cholesterol 7alpha-hydroxylase gene (CYP7A1), a key enzyme in bile-acid biosynthesis, may influence the statin response. To test this hypothesis, a promoter polymorphism (A-204C) in CYP7A1 was examined in 324 hypercholesterolemic patients treated with atorvastatin 10mg. The variant C allele was significantly and independently associated with poor LDL cholesterol reductions; -39% in wild type allele homozygotes, -37% in variant allele heterozygotes, and -34% in variant allele homozygotes (p<0.0001 for trend). Differences were more striking in men, and were enhanced by the coexistence of common variants of apolipoprotein E gene (APOE), epsilon2 or epsilon4. In subjects having wild type alleles at both loci, the mean reduction in LDL cholesterol was -40%, while the value in subjects having two CYP7A1 variant alleles and at least one variant APOE allele was -31% (p<0.0001). Combination analysis of these two loci more accurately predicted the achievement of goal LDL cholesterol, than did both single locus analysis. We concluded that the CYP7A1 A-204C promoter variant was associated with poor response to atorvastatin, which were additively enhanced by common variants in another locus, APOE.     

他汀类药物预处理对不稳定性心绞痛斑块破裂发生的影响

目的 观察冠心病患者在使用他汀类药物后对斑块破裂及不稳定性心绞痛（UAP）发生的影响.方法 采用回顾性病例对照研究方法,分析62例冠心病患者的血脂异常率、他汀类药物治疗率以及治疗后低密度脂蛋白胆固醇（LDL-C）达标率;比较各组冠心病他汀类药物治疗患者的UAP发生率;应用血管内超声（IVUS）测量、分析责任血管狭窄病变处、近端参考血管、远端参考血管外弹力膜截面积、斑块破裂、钙化斑块比例及冠状动脉重构情况.结果 非他汀组患者LDL-C未达标率为96.4%（27/28）,应获得而未得到他汀类药物治疗率为46.4%（13/28）;他汀组患者LDL-C达标率为26.5%（9/34）.他汀组UAP发生率显著低于非他汀组（χ2=34.491,P=0.001）,他汀组LDL-C达标者与未达标者UAP发生率比较差异无统计学意义（χ2=0.002,P=0.968）.他汀组LDL-C显著低于非他汀组（2.457±0.802 vs 3.218±1.130,Z=-9.760,P=0.001）;他汀组未达标患者LDL-C水平显著低于非他汀组未达标患者（2.816±0.640 vs 3.370±0.963,F=-3.613,P=0.001）.他汀组斑块破裂的发生率低于非他汀组（38.2% vs 60.7%,χ2=3.107,P=0.150〉0.05）,正性重构率亦明显低于非他汀组（29.4% vs 46.4%,χ2=1.905,P=0.09〉0.05）.结论 他汀类药物治疗冠心病患者UAP发生率显著降低.使用他汀治疗可使斑块破裂减少,其独立于冠脉重构之外.他汀类药物治疗的最主要效果在于预防动脉粥样硬化斑块的破裂.     

Efficacy and tolerability of ezetimibe 10 mg/day coadministered with statins in patients with primary hypercholesterolemia who do not achieve target LDL-C while on statin monotherapy: A Canadian, multicentre, prospective study--the Ezetrol Add-On Study

BACKGROUND: For patients who have above-target low-density lipoprotein cholesterol (LDL-C) levels while on statin monotherapy, coadministration of a cholesterol absorption inhibitor with the statin may decrease serum LDL-C levels and improve overall lipid profiles. OBJECTIVES: To assess the effectiveness and safety of ezetimibe 10 mg/day coadministered with a statin in patients with primary hypercholesterolemia who have higher than recommended LDL-C levels while on statin monotherapy. METHODS: A six-week, prospective, multicentre study of eligible patients who had above-target LDL-C levels while on monotherapy with any statin, regardless of dose, for a minimum of four weeks. All patients were treated for six weeks with 10 mg ezetimibe daily coadministered with their current statins. RESULTS: A total of 1141 patients were screened, 953 (83.5%) fulfilled the study inclusion criteria and 837 (87.8%) completed the study. Reasons for withdrawal included: lost to follow-up (50 patients [5.2%]); protocol violations (45 patients [4.7%]); adverse events (19 patients [2.0%]); and withdrawal of consent (two patients [0.2%]). After six weeks of treatment, statistically significant (P = 0.001) mean reductions were observed in LDL-C (30.05%), total cholesterol (20.84%), triglycerides (10.16%), apolipoprotein B (19.84%) and the total cholesterol to high-density lipoprotein cholesterol ratio (19.88%). At six weeks, 674 patients (80.5%) achieved target LDL-C levels. Fifty predominantly mild, nonserious adverse events related to ezetimibe were reported by 32 patients (3.4%). Frequently reported adverse events included constipation (n = 7 [0.7% of patients]), diarrhea (n = 4 [0.4%]) and dizziness (n = 4 [0.4%]). CONCLUSION: Ezetimibe coadministered with statins is effective in reducing LDL-C in patients who do not attain target LDL-C levels while on statin monotherapy.     

普伐他汀对急性心肌梗死急诊PCI术后慢性心力衰竭患者疗效的临床研究

目的观察他汀类药物普伐他汀对急性心肌梗死（AMI）急诊经皮冠状动脉介入治疗（PCI）术后慢性心力衰竭患者心功能、外周血肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、基质金属蛋白酶（MMP）-2等的影响。方法将112例AMI急诊PCI术后慢性心力衰竭（NYHA分级Ⅱ～Ⅲ级）患者随机分为普伐他汀20mg组（20mg组）和普伐他汀40mg组（40mg组）。收集患者基本资料,对患者进行心脏超声检查、基本实验室检查、特殊实验室检查（包括炎性因子、MMP-2）、6min步行试验（6-MWT）。随访18个月时再次进行治疗前的各项检测。结果与20mg组比较,40mg组治疗后6-MWT、左心室射血分数（LVEF）显著提高（P〈0．05）;40mg组TNF-d、IL-6、MMP-2治疗后下降水平差值更大（P〈0．05）;普伐他汀治疗后两组患者TNF-α、IL-6、MMP-2改变与总胆固醇,低密度脂蛋白降低之间没有显著相关性。结论普伐他汀对AMI急诊PCI术后慢性心力衰竭患者有益,且这种有益性独立于调脂作用之外。     

Statin therapy is associated with fewer deaths in patients with bacteraemia

Objective Beneficial effects with statin use are increasingly reported in a variety of patient groups. There is in vitro and clinical evidence for its antiinflammatory and immunomodulatory therapeutic roles. We aimed to assess the association between statin administration and mortality in bacteraemic patients.Design A retrospective cohort analysis.Setting A 300-bed acute general hospital.Patients and participants All patients (n=438) requiring hospital care for an episode of bacteraemia during the years 2000–2003 were included. Statin use, patient outcome, and clinical and laboratory variables were collected.Interventions None.Measurements and results There was a significant reduction in all-cause hospital mortality (10.6% vs. 23.1%, p=0.022) and death attributable to bacteraemia (6.1% vs. 18.3%, p=0.014) in patients who were receiving statin therapy at the time of bacteraemia (n=66). The reduction in all-cause hospital mortality (1.8% vs. 23.1%, p=0.0002) and death attributable to bacteraemia (1.8% vs. 18.3%, p=0.0018) was more pronounced in the patients who continued to receive statin therapy after the diagnosis of bacteraemia (n=56). The apparent mortality benefit persisted after controlling for differences between the groups. Statin use prior to admission was associated with a reduced adjusted hospital mortality rate (odds ratio 0.39; CI 95% 0.17, 0.91; p=0.029), and continuing statin use after bacteraemia increased this effect (odds ratio 0.06; CI 95% 0.01, 0.44; p=0.0056).Conclusion This retrospective study demonstrates a significant survival benefit associated with continuing statin therapy in bacteraemic patients. The potential for statins as an adjuvant therapy in sepsis warrants further investigation.Electronic Supplementary Material Supplementary material is available in the online version of this article at Work was performed at Ipswich Hospital (Ipswich) and Princess Alexandra Hospital (Brisbane), Australia.This article refers to the editorial at .The authors have no financial interest in the products discussed in this paper. The authors have not received sponsorship or funding or have any conflicts of interest.     

Stroke severity and outcomes for octogenarians receiving statins

Pre-exposure to 3-hydroxy-3-methylgutaryl-coenzyne A reductase inhibitors (statins) appears to improve outcomes in patients with acute ischemic stroke (AIS). Whether this extends to patients over 80 is not known. Patients ≥80 years of age with AIS were retrospectively reviewed from the stroke registry of a tertiary stroke center. Pre-admission statin use, demographics, vascular risk factors, and comorbid conditions were assessed. Primary outcomes were admission National Institutes of Health Stroke Scale (NIHSS) scores and in-hospital mortality/discharge to hospice, and secondary outcomes included subsequent intracerebral hemorrhage (ICH) and modified Barthel index (mBI) at 3 months. Multivariable logistic regression was used to evaluate the association between pre-admission statin use and outcomes among elderly patients. Among 804 patients ≥80, those taking statins prior to AIS admission were overall younger, were more likely to have hypertension, coronary artery disease, diabetes, hyperlipidemia, and were more likely to be on an antiplatelet, but less likely to receive treatment with IV tissue plasminogen activator (tPA). Patients on statin had lower stroke severity (NIHSS > 16: 21.9% vs. 27.6%) and in-hospital mortality/discharge to hospice (22.8% vs. 27.6%), but neither was significant. There was no difference in ICH (1.2% vs. 1.9%), and patients on statins had a non-significant trend toward less disability on mBI (27.5% vs. 35.7%). Pre-admission statin use did not show a statistical difference in either outcome, but it did show a trend toward lower stroke severity and improved short-term outcomes. In addition, our study suggests that statins may be safe in elderly stroke patients and may not increase the risk of ICH.