荟萃分析对多样本临床试验结果重现率分析

探讨应用多样本临床试验荟萃分析进行药物和治疗方案有效性和安全性研究。方法：本文采用荟萃分析,一种非参数方法,评价临床试验结果的重现率,用于对充血性心脏衰竭,ＣＨＦ伴心性死亡,ＣＨＦ伴其他原因死亡病例,对给予血管紧张素转化酶抑制剂治疗组和给安慰剂组各自的相对率和超常率的分析。     

血管紧张素转换酶抑制剂治疗慢性充血性心力衰竭有效剂量探讨

目的探讨不同剂量血管紧张素转换酶抑制剂（ACEI）卡托普利治疗慢性充血性心力衰竭（CHF）疗效。方法CHF患者56例，随机分为卡托普利高剂量组n=28，150mg／d，低剂量组n=28，25mg／d，疗程24周。观察治疗前后两组临床症状、超声心动图心功能指标并记录不良反应发生情况。结果高剂量组总有效率89．3％，明显优于低剂量组60．7％（P〈0．01），左心室功能指标每搏量（SV）、心排出量（CO）、射血分数（EF）、左室短轴缩短率（FS）治疗后与治疗前比较，高剂量组有显著改善（P〈0．01），低剂量组变化不大（P〉0．05）。结论大剂量（目标剂量）ACEI较小剂量更有效改善心功能。     

雷米普利对心肌梗死后心脏血管紧张素受体基因转录的影响(英文)

在慢性给予血管紧张素转换酶抑制剂雷米普利后的大鼠中观察心肌梗死（ＭＩ）后早期心肌组织中血管紧张素 Ⅱ（ Ａｕｇ Ⅱ）受体基因转录的改变．方法：通过冠状动脉结扎建立大鼠ＭＩ模型,手术前１周即开始给予雷米普利或水,术后在存活大鼠中继续治疗至处死大鼠;用定量ＲＴ－ＰＣＲ法检测大鼠心间隔组织的Ａｎｇ Ⅱ受体ｍＲＮＡ水平．结果：大鼠ＭＩ后心间隔组织中ＡＴ１和ＡＴ２受体ｍＲＮＡ水平升高,在１ｄ时达到高峰．给予雷米普利的大鼠ＭＩ后心间隔组织中Ａｎｇ Ⅱ受体ＩｎＲＮＡ水平与给予水的大鼠相比无显著差别．结论：非梗死区心肌组织中 Ａｎｇ Ⅱ受体基因转录的特征性改变可能与ＭＩ后心肌重构过程有关而与ＡＣＥ抑制无关．     

缬沙坦联合依那普利治疗充血性心力衰竭疗效观察

目的:探讨缬沙坦和依那普利联合应用与单用依那普利治疗充血性心力衰竭(CHF)的疗效。方法:对73例住院或门诊CHF患者随机分成2组,在给予常规洋地黄、利尿剂、血管扩张剂等基础治疗的同时,分别加用依那普利及缬沙坦和单用依那普利治疗,疗程8周,观察治疗前后心率(HR)和血压(Bp)、心胸比率、左室收缩和舒张末期内径(LVD s、LVDd)、左室射血分数(LVEF)及心功能的变化。结果:两组治疗后的LVEF均明显增高,差异均具有显著性(P<0.05),组间比较具有极显著性差异(P<0.01)。无明显药物不良反应。结论:缬沙坦和依那普利联合应用较单用依那普利治疗CHF疗效好、安全合理。     

ACE抑制剂群多普利的药理与临床新进展

ＡＣＥ抑制剂群多普利的药理与临床新进展吴苏澄，贺林（成都军区总医院药剂科成都６１００８３）群多普利（ｔｒａｎｄｏｌａｐｒｉｌ）为不含巯基的血管紧张素转换酶（ＡＣＥ）抑制剂。ＰＯ给药具降压活性，且作用持续时间长，不影响心输出量，是一种真正的每天ＰＯ一次...     

ACE—Ⅰ在高血压充血性心力衰竭治疗中的作用

高血压患者发生龙血性心力衰竭的机制上要是左心室肥厚合并冠心病和肥胖等因素，引起收缩功能和舒张功能障碍。血管紧张素转换酶抑制剂（ACD－I）在降低血压的同时，减少上心室质量指数的作用更有效。其能改善异常功能（肾脏和心血管）和异常结构（心肌重构），明显降低住院率和死亡率。1资料和方法1．1临床资料我院近5年来收治的68例高血压心力衰竭的患者，平均年龄（64．2±1）岁，随机分成两组，年龄，发病情况，机体状态等因素无灵苦差异。其中，治疗组36人男：女=1．7：1：对照组32人，男：女=1：3．1．2治疗方法对照组常现应用洋地…     

新型血管紧张素转换酶抑制剂喹那普利

喹那普利是一个新型的血管紧张素转换酶抑制剂,作用较卡托普利和依那普利为强,尚有额外的降脂作用。喹那普利无肾脏毒性作用,不易蓄积中毒,不良反应小而轻微,可作为高血压和心力衰竭的首选药物。     

血管紧张素(1-7)的心血管效应

血管紧张素(1-7)是RAAS重要的生物活性物质之一,具有扩血管、抗增殖和抗凝血等效应,能拮抗血管紧张素Ⅱ等物质的生物活性。它可经血管紧张素Ⅰ、Ⅱ转化而来。血管紧张素转换酶2是Ang(1-7)的限速酶。Ang(1-7)主要通过其G-蛋白偶联受体Mas产生作用。     

血管紧张素转换酶D等位基因与高血压性肾损害的探讨(附122例分析)

目的探讨血管紧张素转换酶(ACE)基因多态性是高血压病(EH)的致病基因,还是EH性肾损害的危险因素。方法四角分析法研究ACE基因多态性与EH的关系,采用PCR方法对比,有和无尿微量蛋白增高,EH组与对照组ACE多态性的差异。结果无论有还是没有EH家族史的EH组(n=122)和对照组(n=109)ACE基因插入／缺失(I／D)多态性之间的变化均无显著性差异。伴有尿微量蛋白增高EH患者收缩压和甘油三脂最高,靶器官损害多,D等位基因人数也最多。结论ACE基因多态性与EH发生关系不大,但D等位基因可能增加EH性肾损害的危险。     

洛沙坦的药理学及临床应用

洛沙坦对血管紧张素Ⅱ受体AT1亚型有选择性拮抗作用,副作用少,用于高血压、充血性心力衰竭的治疗:本文介绍洛沙坦的药理作用、药代动力学特点和临床应用。     

Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta-analysis of 36 clinical trials

Aims

Congestive heart failure (CHF) associated with vascular endothelial growth factor tyrosine-kinase inhibitors (VEGFR-TKIs) has emerged as a relevant problem in clinical and scientific communities. We performed an up-to-date, comprehensive meta-analysis to determine the overall incidence and risk of CHF in cancer patients receiving VEGFR-TKIs.

Methods

The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to August 31 2013 were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.

Results

A total of 10 553 patients from 36 clinical trials were included. The overall incidence of all grade and high grade CHF associated with VEGFR-TKIs was 3.2% (95% CI 1.8%, 5.8%) and 1.4% (95% CI 0.9%, 2.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all grade (OR 2.37, 95% CI 1.76, 3.20, P < 0.001) and high grade (OR 3.51, 95% CI 1.74, 7.05, P < 0.001) CHF. In subgroup analyses, the risk of CHF did not significantly vary with tumour types (P = 0.071 for all grade; P = 0.72 for high grade) and VEGFR-TKIs (P = 0.55 for all grade; P = 0.99 for high grade). Meta-regression indicated that CHF might possibly occur early in the treatment of VEGFR-TKIs. No evidence of publication bias was observed.

Conclusion

The use of VEGFR-TKIs is associated with a significantly increased risk of developing congestive heart failure in cancer patients. Clinicians should be aware of this risk and provide close monitoring in patients receiving these therapies.     

ACEI在慢性心力衰竭药物治疗中应用现状调查分析

目的:分析慢性心力衰竭治疗中血管紧张素转换酶抑制剂(ACEI)的使用情况,了解其应用现状及其与治疗指南之间的差距及产生差距的原因。方法:调查住院及门诊患者的病因、心功能分级(NYHA)、血压、心率、左室射血分数、有无用药禁忌证、ACEI的使用剂量和时间、停药或减量的原因等,将门诊和住院病例分别按年龄(≥65岁,<65岁)、性别(男、女)、血压(>140mmHg,≤140mmHg)、心率(≥90次/min,<90次/min)、左室射血分数(>40%及≤40%)、心功能(Ⅱ、Ⅲ、Ⅳ)、病因、合并症分组,分析比较ACEI使用率和使用剂量。结果:住院患者ACEI的使用率为79.2%,其中91.3%达到治疗指南要求的靶剂量;门诊患者ACEI总的使用率为60.1%,75.2%达到治疗指南要求的靶剂量;血压、性别、合并肾功能不全等因素对ACEI的使用有显著影响。结论:ACEI在慢性心力衰竭的治疗与治疗指南尚有一定差距。     

Endothelin receptor antagonists in cardiology clinical trials

Endothelin-1 (ET-1) is enhanced and has been demonstrated to be a prognostic marker in patients with advanced stages of heart failure, acute ischaemic syndromes, myocardial infarction and pulmonary hypertension. Activation of the endothelin (ET) system is associated with adverse haemodynamic consequences in patients with congestive heart failure and results in coronary vasoconstriction in patients with coronary artery disease (CAD). Moreover, ET-1 raises blood pressure, induces vascular and myocardial hypertrophy and acts as the natural counterpart of nitric oxide (NO), which exerts vasodilating, antithrombotic and antiproliferative effects. This article reviews recently completed and ongoing clinical trials examining the effects of ET receptor antagonists in patients with heart failure, CAD, arterial hypertension and pulmonary hypertension.     

Measuring beneficial and adverse events in osteoarthritis clinical trials

Outcome assessment in osteoarthritis (OA) clinical trials is dependent on the use of valid, reliable, and responsive measurement procedures. The measurement of antirheumatic drug efficacy currently lacks international standardization, and current guidelines are not in complete agreement. There remains an urgent need to agree on a core set of outcome measures for hip OA, knee OA, hand OA and generalized OA clinical trials. A degree of harmonization has been achieved in the measurement of adverse events using the WHO and COSTART systems. However, different methods of eliciting adverse events result, in different event rate scores. The optimum method of assessing beneficial and adverse events in OA clinical trials has yet to be elucidated but is the subject of ongoing research and discussion.     

Clinical trials and tribulations

1. Pharmacologists should be involved in all stages of drug development. Often neglected is the final step, the clinical trials and other studies that determine clinical utility. The present article illustrates how pharmacoepidemiology can facilitate evaluation of the clinical potential of different drugs used to treat hypertension. 2. The evidence base for the drug treatment of hypertension is very strong. Large-scale outcome trials, largely based on diuretics, indicate that stroke events are prevented to the extent expected from blood pressure reduction, but there appears to be a shortfall in the prevention of coronary heart disease events. 3. On theoretical grounds, newer agents may be expected to have benefits in coronary heart disease prevention beyond blood pressure reduction. Recent trials with angiotensin-converting enzyme inhibitors and calcium channel blockers suggest no advantage over conventional drugs, but shortcomings in these studies mean that each is uninformative. 4. Observational studies based on pharmacoepidemiological principles offer an alternative approach to evaluating outcomes in treated hypertensives. 5. Evidence from the Glasgow Blood Pressure Clinic database suggest that there are outcome differences between antihypertensive agents. Angiotensin-converting enzyme inhibitor treatment is associated with a mortality advantage, whereas calcium channel blocker therapy is associated with a poorer prognosis. Preliminary findings from a primary care database support these observations. 6. Long-term follow up of a well-documented high-risk clinical population may allow detection of outcome differences not apparent in relatively short-term clinical trials. 7. Appropriate interpretation of observational data necessitates an understanding of the strengths and limitations of observational data. Clinical pharmacologists have a critical role in design and evaluation of pharmacoepidemiology studies.     

The effect of beta-blocker therapy on quality of life in heart failure patients: a systematic review and meta-analysis

PURPOSE: To assess the impact of beta-blocker therapy on quality of life (QoL) in chronic heart failure (CHF) patients receiving optimal standard medication. METHODS: Randomised controlled trials (RCT) assessing QoL with a generic or disease specific instrument were identified by searching Medline, Embase, Pascal, Cochrane Controlled Trial database, and the bibliographies of the published articles. Studies published between 1985 and 2002 were included, regardless of language of publication. Cochrane Review Manager 4.2 software was used to analyse the data and standardised mean difference (SMD) was calculated to assess the effect on QoL. RESULTS: A total of 9 trials involving 1954 patients fit into the inclusion criteria for the analysis. QoL improved more in the beta-blocker group compared to the control arm, but the SMD did not reach statistical significance (SMD, 0.07; 95%CI [-0.16, 0.02]; p = 0.13). Subgroup analysis, per type of beta-blocker and various treatment follow-up showed similar results. CONCLUSIONS: In this meta-analysis there is evidence that beta-blocker therapy, on top of standard medication, does not impair QoL. Clinicians may add beta-blockers to standard therapy without concerns of impairing QoL in patients with CHF.     

Meta-analysis of clinical trials: Summary of an international conference

Summary An international conference of clinicians, clinical investigators and biostatisticians discussed meta-analysis in relation to clinical trials, i.e. the combination of data from separate studies for the purpose of obtaining information that cannot be derived from the individual studies.Meta-analysis can be a helpful tool for generating hypotheses for future trials, for studying the consistency of trials of the same or similar goals, and for generating more precise estimates of effect. There are still a number of unresolved questions about the methodology and interpretation of meta-analysis. Better and more uniform reporting of primary studies would increase the usefulness of meta-analysis.     

Ongoing clinical trials in systemic hypertension

Hypertension was identified as a cardiovascular risk factor in the late fifties and still remains a public health issue. The number of patients treated reaches only half of those diagnosed and, of those treated, half fail to reach target blood pressure. Furthermore, the number of antihypertensive drugs reaching the market has increased exponentially in the last few years, however, the impact on treatment and on attaining target blood pressure levels remains to be seen. The high percentage of treated patients who do not reach target blood pressure, combined with the high number of patients requiring more than one antihypertensive drug, have triggered a series of long-term morbidity and mortality trials comparing different therapeutic approaches (‘new’ pharmacological classes vs. ‘old’ pharmacological classes). These are described in this paper.     

某院药物临床试验不良事件监控质量调查

目的:分析及评价某院药物临床试验不良事件监控质量.方法:对照不良事件监控的质量评分标准,调查2007-2013年结题的Ⅱ~Ⅲ期项目中不良事件监控的质量得分及各要素的年均得分率.并对2007-2013年发生的15例严重不良事件(SAE)监控情况进行分析.结果:总体上,某院药物临床试验不良事件监控质量得分及各要素得分率均呈现逐年增长的趋势.2011年某院针对不良事件的监控实施展开全面整改工作,整改前存在的问题主要集中在:启动会培训缺失或不完整、实验检查类不良事件收集的遗漏、SAE获知的滞后性、SAE报告表原件的遗失、不良事件源文件记录的缺失或不完整.通过完善规章制度、建立应急预案、强化伦理审查力度、强化试验前不良事件的预防措施、加强机构办公室及科室的监控力度等措施,某院不良事件的监控质量显著提高.结论:加强临床试验机构对不良事件的监控作用,依靠临床试验各部门的共同努力,不断完善安全性监控体系,才能提高临床试验的质量和水平.