Comparison of Antiplatelet Effect and Safety of Clopidogrel Napadisilate with Clopidogrel Bisulfate in Coronary Artery Disease Patients: Multi-center, Randomized, Double-blind, Phase IV, Non-inferiority Clinical Trial

Background

Clopidogrel napadisilate has better clopidogrel stability than clopidogrel bisulfate. There are no data, however, on the antiplatelet efficacy and tolerability of clopidogrel napadisilate in coronary artery disease (CAD) patients.

Objective

The aim of this study is to demonstrate that the combination therapy of aspirin and clopidogrel napadisilate is not inferior to that of aspirin and clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation, if it is given for 4 weeks to CAD patients who had been treated with a drug-eluting stent more than 12 months prior and had remained in a stable condition with a single antiplatelet agent, aspirin.

Methods

This study was a prospective, randomized, double-blind, double-dummy, parallel-group, phase IV clinical trial. A total of 162 patients were prospectively recruited from three centers. The subjects were randomized to either the test group that was treated with 75 mg of clopidogrel napadisilate once daily or to the control group that was treated with 75 mg of clopidogrel bisulfate once daily. The primary outcome was the percent inhibition of the platelet aggregation change after the medication, as assessed by a VerifyNow? P2Y12 assay. The secondary outcome was the change in P2Y12 reaction units (PRUs) from the baseline to the end of 4 weeks of treatment. The prevalence of adverse events was assessed at each visit through a direct interview.

Results

The mean increase in the percent inhibition after 4 weeks of treatment was 19.4 % in the clopidogrel napadisilate group and 19.5 % in the clopidogrel bisulfate group. The lower bound of the 95 % two-sided confidence interval for the difference in the change between the two groups (-5.46) was greater than the pre-defined non-inferiority margin of (-10.5). Therefore, clopidogrel napadisilate was deemed non-inferior to clopidogrel bisulfate with respect to its effectiveness in inhibiting platelet aggregation. The PRU decreased by 73.1 ± 30.7 in the clopidogrel napadisilate group, which decreased by -7.8 more than in the clopidogrel bisulfate group (65.3 ± 62.1); but the difference between the two groups was statistically insignificant (p = 0.435). There was no significant difference in the drug-related adverse events between the two groups (12.3 vs. 10.1 %; p = 0.804).

Conclusion

The platelet inhibitory efficacy of clopidogrel napadisilate is not inferior to that of clopidogrel bisulfate. There were also no statistically significant differences between the two treatment groups in the safety analyses. Therefore, clopidogrel napadisilate can be a suitable alternative to clopidogrel bisulfate in stable CAD patients who have undergone a drug-eluting stent placement.

Clinical Trial Registration

Registered at ClinicalTrials.gov as NCT01830491.     

蛭芎胶囊联合氯吡格雷治疗缺血性脑卒中的临床研究

目的探讨蛭芎胶囊联合氯吡格雷治疗缺血性脑卒中的临床疗效。方法:选取2015年05月—2018年05月在河南科技大学附属许昌市中心医院治疗的缺血性脑卒中患者110例,随机分为对照组(55例)和治疗组(55例)。对照组口服硫酸氢氯吡格雷片,1片/次,1次/d。治疗组在对照组的基础上口服蛭芎胶囊,4粒/次,3次/d。两组患者均连续治疗2周。观察两组患者临床疗效,同时比较治疗前后两组患者神经功能缺损程度(NIHSS)和日常生活能力(ADL)评分,以及内皮素1(ET-1)和一氧化氮(NO)水平。结果:治疗后,对照组临床有效率为83.64%,显著低于治疗组的94.55%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者NIHSS评分和血清ET-1水平显著降低(P0.05),而ADL评分和血清NO水平显著升高(P0.05),且治疗组改善程度比对照组更为显著(P0.05)。结论:蛭芎胶囊联合氯吡格雷治疗缺血性脑卒中,能够改善血管内皮功能及血液高凝状态,提高神经功能及生活质量。     

Clinical impact of early clopidogrel discontinuation following acute myocardial infarction hospitalization or stent implantation: analysis in a single integrated health network

ABSTRACT

Objective: To determine the association between the discontinuation of clopidogrel therapy prior to 1 year and the risk of acute myocardial infarction (AMI) hospitalization, coronary intervention or all-cause mortality in a cohort of managed-care patients following AMI hospitalization or stent insertion.

Research design and methods: This observational cohort study included 1152 patients enrolled in the Health Alliance Plan who were hospitalized for AMI, or who underwent coronary stent placement. Clopidogrel use was assessed using pharmacy claims data. The association between discontinuation of clopidogrel prior to 1 year following the initial ACS event and the primary outcome of AMI hospitalization/procedure was assessed using Cox proportional hazards models. Additionally, an analysis was conducted to determine the association of discontinuation prior to 1 year with a secondary composite outcome of AMI hospitalization/coronary stent procedure or all-cause mortality.

Main outcome measures: The primary outcome was AMI hospitalization or procedure. The secondary outcome was a composite of AMI hospitalization/ procedure, or all-cause mortality.

Results: Discontinuation of clopidogrel in the total cohort of patients was associated with a significantly higher risk of the primary outcome of AMI hospitalization/ coronary intervention (HR 2.712, 95% CI 1.634–4.502). Consistent with this finding, discontinuation of clopidogrel was also associated with a significantly higher risk of the secondary composite endpoint (HR 1.844, 95% CI 1.281–2.653).

Conclusions: In patients enrolled in an integrated health network, clopidogrel discontinuation prior to 1 year following AMI hospitalization or stent placement is associated with adverse outcomes including greater risk of death, AMI hospitalization or coronary intervention. These results should be interpreted within the context and limitations of observational research, which cannot attribute causality.     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

HPLC法测定硫酸氢氯吡格雷片中氯吡格雷含量的不确定度评定

目的：建立HPLC法测定硫酸氢氯吡格雷片中氯吡格雷含量不确定度的评定方法。方法：通过建立HPLC法测定含量的数学模型,分析影响不确定度的因素,并对各个不确定度分量进行评估。结果：硫酸氢氯吡格雷片中氯吡格雷含量测定的合成不确定度为0.5%;扩展不确定度为1.0%;测定结果为（101.0±1.0）%。结论：该法可用于HPLC法测定硫酸氢氯吡格雷片中氯吡格雷含量的不确定度评估。     

The efficacy and safety of clopidogrel resinate as a novel polymeric salt form of clopidogrel

A novel polymeric salt of clopidogrel, clopidogrel resinate, was prepared as a anticoagulant drug. To prove the feasibility as a new active substance, clopidogrel resinate was evaluated for its efficacy and safety. In accelerated stability tests, the clopidogrel resinate tablet (Pregrel) showed less brown discoloration and fewer impurities than the clopidogrel bisulfate tablets under open and closed conditions. In toxicity tests, no deaths occurred after a single dose of up to 2000 mg/kg/day and 13-week repeated doses of up to 625 mg/kg/day in rats without abnormal symptoms compared to clopidogrel bisulfate. When clopidogrel resinate was treated onto Caco-2 cell monolayers, clopidogrel, but not the resin, permeated across the cells with a hight permeation coefficient (Papp) of 13.5 +/- 1.13 x 10(-6) cm/sec. Clopidogrel resinate and clopidogrel bisulfate showed similar pharmacokinetics following oral administration to beagle dogs. A single oral administration of clopidogrel resinate dose-dependently inhibited ADP-induced ex vivo aggregation up to 30 mg/kg in rats. In conclusion, clopidogrel resinate was proved to be an efficient and safe polymeric salt as a candidate for a new clopidogrel salt.     

Effect of ranitidine on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel

ABSTRACT

Objective: Clopidogrel is an oral thienopyridine antiplatelet agent indicated for the treatment of atherothrombotic events in patients with acute coronary syndrome (ACS). Prasugrel, a novel oral thienopyridine, is under investigation for the reduction of atherothrombotic events in patients with ACS undergoing percutaneous coronary intervention. Prasugrel's solubility decreases with increasing pH, suggesting that concomitantly-administered medications that increase gastric pH may lower the rate and/or extent of prasugrel absorption. This study evaluated the influence of ranitidine coadministration on the pharmacokinetics and pharmacodynamics of the respective active metabolite of prasugrel and clopidogrel.

Research design and methods: In this open-label, two-period, two-treatment, crossover study, 47 healthy male subjects were randomized to one of two study arms, receiving either prasugrel (60-mg loading dose [LD], 10-mg maintenance dose [MD] for 7?days; n?=?23) or clopidogrel (600-mg LD, 75-mg MD for 7?days; n?=?24). In one treatment period, subjects received prasugrel or clopidogrel alone, and in the alternate period received the same thienopyridine with ranitidine (150?mg twice daily, starting 1?day before the LD). Pharmacokinetic parameter estimates (AUC_{0?t last}, C_max, and t_max) and inhibition of platelet aggregation (IPA) by light transmission aggregometry were assessed at multiple time points after the LD and final MD.

Results: Ranitidine had no clinically significant effect on the area under the plasma-concentration-time curve (AUC) and did not affect the time to C_max (t_max) for active metabolites of either prasugrel or clopidogrel. It reduced the geometric mean maximum concentrations of active metabolite (C_max) after a prasugrel and clopidogrel LD by 14% and 10%, respectively, but these differences were not statistically significant. When coadministered with a 60-mg prasugrel LD, ranitidine did not affect the time to, or magnitude of, peak IPA, but did result in a modest reduction at 0.5?h from 67.4 to 55.1% (p?<?0.001). Ranitidine did not affect prasugrel IPA during MD. For clopidogrel, IPA was not affected by ranitidine. Prasugrel and clopidogrel were both well-tolerated, with/without ranitidine.

Conclusions: Results from this study suggest that there is no significant drug–drug interaction between oral ranitidine therapy and concomitantly-administered prasugrel or clopidogrel.     

Cost-effectiveness of clopidogrel treatment in percutaneous coronary intervention: a European model based on a meta-analysis of the PCI-CURE,CREDO and PCI-CLARITY trials*

ABSTRACT

Objective: Our objective was to conduct a comprehensive cost-effectiveness analysis of pre-treatment and long-term treatment with clopidogrel in percutaneous coronary intervention (PCI) in three European countries based on a meta-analysis of the PCI-Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel for the Reduction of Events During Observation (CREDO) and PCI-Clopidogrel as Adjunctive Therapy (CLARITY) trials. This analysis adds to existing knowledge by providing further data on the cost-effectiveness of clopidogrel in PCI across a wide spectrum of patients.

Methods: A combined decision tree and Markov model was created. The relative risks of myocardial infarction, cardiovascular death and of major bleedings with clopidogrel were based on a fixed-effects meta-analysis. The risk of ischaemic events in untreated patients and long-term survival were taken from the Swedish hospital and death registers. A societal perspective was used in Sweden and a payer perspective in Germany and France. Costs are stated in €2006 and effectiveness measured in quality-adjusted life-years (QALYs).

Results: The pooled effects of clopidogrel on the combined endpoint showed a relative risk of 0.711 (p = 0.003) at 30 days and 0.745 (p = 0.002) at end of follow-up (up to 1 year). Pre-treatment with clopidogrel compared with aspirin alone is a dominant strategy. Long-term treatment with clopidogrel compared with 1-month treatment leads to approximately 0.09 QALYs at an incremental cost of €393 in Sweden, €709 in Germany and €494 in France. The corresponding incremental cost-effectiveness ratios range from €4225/QALY to €7871/QALY.

Conclusion: The results of this modelling analysis suggest that pre-treatment and long-term treatment in PCI with clopidogrel for up to 1 year are cost-effective in a range of patient groups and settings given commonly accepted thresholds.     

Clinical impact of early clopidogrel discontinuation following acute myocardial infarction hospitalization or stent implantation: analysis in a nationally representative managed-care population

ABSTRACT

Objectives: To evaluate the association between discontinuation of clopidogrel therapy and risk of acute myocardial infarction (AMI) hospitalization or cardiac revascularization in a nationally-representative patient population following hospitalization for an AMI or coronary stent insertion.

Research design and methods: This observational cohort study was performed using data on patients from the PharMetrics Anonymous Patient-Centric Database who were hospitalized for an AMI or coronary stent insertion and subsequently treated with clopidogrel. Cox proportional hazard modeling was used to evaluate the association between clopidogrel discontinuation prior to 1 year post-initial AMI hospitalization and the primary endpoint of repeat AMI hospitalization or coronary intervention defined as percutaneous coronary intervention (PCI) with or without stent, or coronary artery bypass graft (CABG).

Main outcome measures: The main outcome for this study was AMI hospitalization or coronary intervention defined as PCI with or without stent placement or CABG.

Results: A total of 31?835 patients were included in the analyses. Patients were predominantly male and the average patient age was approximately 60 years. After controlling for baseline patient characteristics and follow-up time, discontinuation of clopidogrel was associated with a significantly higher rate of hospitalization for AMI or coronary intervention (HR 1.34, 95% CI 1.22–1.44).

Conclusion: Within a population of ACS patients drawn from a database of 85 US health plans, clopidogrel discontinuation within 1 year following hospitalization for AMI or stent placement is associated with an increased risk of AMI hospitalization or coronary intervention. The results of this study should be interpreted within the context of observational research, which does not address cause and effect relationships.     

Clopidogrel Bisulfate

Clopidogrel bisulfate (hereafter, clopidogrel), a selective inhibitor of ADP-induced platelet aggregation, is approved for the reduction of atherothrombotic events in patients with ST-segment elevation myocardial infarction (STEMI). In COMMIT/CCS-2, a well designed trial in 45,852 adult patients with STEMI, relative to aspirin alone, clopidogrel 75 mg/day plus aspirin treatment significantly reduced the risk of both coprimary endpoints: the composite endpoint of reinfarction, stroke, or death from any cause and the risk of death from any cause. Based on the findings of this trial, treating 1000 patients for approximately 2 weeks with clopidogrel is associated with nine fewer patient deaths, reinfarctions, or strokes during treatment. In CLARITY-TIMI 28, a well designed supportive study in 3491 adult patients with STEMI, clopidogrel plus aspirin reduced the odds that a composite primary endpoint event of an occluded infarct-related artery, recurrent myocardial infarction, or death from any cause would occur versus aspirin plus placebo. Clopidogrel treatment was generally well tolerated in these clinical trials, with no significant between-group difference in the rate of major bleeding in either trial. Experience in other patient populations (e.g. those with recent myocardial infarction, recent ischemic stroke, or established peripheral arterial disease) has shown that longer-term (< or =3 years) clopidogrel monotherapy is generally well tolerated.     

硫酸氢氯吡格雷的临床应用进展

目的本文对近年来硫酸氢氯吡格雷在临床上的应用进展进行了综述.硫酸氢氯吡格雷适用于心肌梗塞、中风等心脑血管疾病,与其它药物联合应用比单用一种药物有更好疗效,国产与进口产品疗效相似.     

氯吡格雷联合阿司匹林治疗短暂性脑缺血发作的疗效及安全性研究

目的探讨氯吡格雷联合阿司匹林在短暂性脑缺血发作中的疗效及安全性。方法选取60例TIA患者,随机分为两组,对照组予小剂量阿司匹林,观察组则在对照组予氯比格雷,比较两组的疗效及用药安全性。结果观察组总有效率达90.0%,与对照组的总有效率73.3%比较,差异有统计学意义(P<0.05)。观察组治疗后发作时间均较治疗前及对照组缩短更明显,差异有统计学意义(P<0.05)。结论氯吡格雷联合阿司匹林治疗短暂性脑缺血发作能明显减少发作时间,改善患者的临床症状,安全性好,值得推广和应用。     

阿加曲班联合硫酸氢氯吡格雷对急性后循环缺血性脑卒中患者凝血功能、NIHSS评分和BI指数的影响

目的 观察新型凝血酶抑制剂阿加曲班联合抗血小板药硫酸氢氯吡格雷对急性后循环缺血性脑卒中患者血液高凝状态、血小板（PLT）计数、美国国立卫生研究院卒中量表（NIHSS）评分和Barthel指数（BI）的影响。方法 回顾性选取2020年9月-2021年8月揭阳市人民医院神经内科诊治的急性后循环缺血性脑卒中患者70例为研究对象,根据治疗方法分为对照组和试验组,每组各35例,两组患者的血压、血糖都严格依照急性缺血性脑卒中治疗指南予以监测管理,同时使用稳定斑块等药物。对照组口服硫酸氢氯吡格雷片,每次75 mg,每天1次,持续服用14 d。试验组在对照组基础上加用阿加曲班注射液,在开始治疗的第1~2天,阿加曲班注射液60 mg加入至0.9%氯化钠注射液380 mL中,输液泵泵入,24 h持续不间断静脉输注,从第3天起,阿加曲班注射液10 mg加入至0.9%氯化钠注射液250 mL中,输液泵泵入,持续3 h静脉输注,间隔12 h再输注1次,持续用药5 d,阿加曲班注射液共用药7 d。采用NIHSS评分评估两组患者的神经缺损程度,采用BI指数评估两组患者日常生活自理能力。动态检测两组患者凝血三项[凝血酶时间（TT）、凝血酶原时间（PT）、活化部分凝血酶原时间（APTT）]和血小板计数（PLT）。观察记录用药过程中两组患者不良反应发生情况。结果 治疗14 d,试验组总有效率91.43%,对照组总有效率68.57%,两组比较差异有统计学意义（P<0.05）。治疗前,两组患者NIHSS评分及BI指数比较,差异无统计学意义（P>0.05）。治疗后两组患者NIHSS评分均较治疗前明显降低（P<0.05）,且治疗后试验组NIHSS评分显著低于对照组（P<0.05）;治疗后两组患者BI指数均较治疗前明显升高（P<0.05）,且治疗后试验组BI指数显著高于对照组（P<0.05）。与用药前和对照组相比,试验组在应用阿加曲班注射液第1天（60 mg·d^-1）,TT、PT、APTT均明显延长（P<0.05）;用药第3天,即减量为20 mg·d^-1,TT、PT、APTT较用药第1天均明显缩短（P<0.05）,但较治疗前和对照组有所延长（P<0.05）;停药第2天,TT、PT、APTT均恢复至治疗前水平。PLT在阿加曲班注射液用药前、用药期间（60 mg·d^-1、20 mg·d^-1）、停药后无明显变化,差异无统计学意义（P>0.05）。对照组凝血三项和PLT在各检测时间点均无明显变化,差异无统计学意义（P>0.05）。两组患者在治疗期间未发生过敏性休克、出血、心律失常等与治疗药物相关的不良反应。结论 阿加曲班注射液联合硫酸氢氯吡格雷能够有效抑制血栓形成而不影响正常的凝血功能,明显改善急性后循环缺血性脑卒中患者的高凝状态,抗血栓再次形成能力强,安全性好;患者神经功能缺损情况明显改善,日常独立生活能力得到提高,病情得到有效控制。阿加曲班注射液联合硫酸氢氯吡格雷是一种有效的治疗急性后循环缺血性脑卒中方法,有较高的临床推广应用价值。     

Drug evaluation of clopidogrel in patients with ischemic stroke

Clopidogrel is an effective antiplatelet medication used for the secondary prevention of ischemic events in patients with various cardiovascular, cerebrovascular and peripheral vascular disease conditions. The objective of this paper is to discuss the role of clopidogrel in ischemic stroke patients and to review the existing data from randomized trials supplemented by pilot and mechanistic studies that supports these indications for its use. An analysis of the mechanism of action and pharmacology of clopidogrel is provided. After Phase III trials, such as the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients) trials, the role of clopidogrel in secondary prevention is well defined. The role of clopidogrel in acute ischemic stroke and neurointerventional procedures is evolving based on new pilot trials. At present, there is insufficient data to recommend the use of clopidogrel in acute ischemic stroke. Clopidogrel may be a valuable alternative to aspirin. However, more studies are required to assess the role of clopidogrel in selected patient groups with respect to acute ischemic stroke.     

通塞脉片联合氯吡格雷治疗急性脑梗死的临床研究

目的 探讨通塞脉片联合硫酸氢氯吡格雷片治疗急性脑梗死的临床疗效。方法 选取2020年1月—2023年3月阜阳市中医医院收治的108例急性脑梗死患者,按随机数字法将患者分对照组（54例）和治疗组（54例）。对照组患者口服硫酸氢氯吡格雷片,75 mg/次,1次/d。在对照组的基础上,治疗组口服通塞脉片,5片/次,3次/d。两组患者均治疗14 d。观察两组患者临床疗效,比较治疗前后两组患者症状好转时间,美国国立卫生研究院卒中量表（NIHSS）和Fugl-Meyer运动功能表（FMA）评分,血清炎性因子白细胞介素-6（IL-6）和同型半胱氨酸（Hcy）水平及不良反应。结果 治疗后;治疗组患者总有效率（98.15%）明显高于对照组（83.33%,P＜0.05）。治疗后,治疗组症状好转时间均早于对照组（P＜0.05）。治疗后,两组NIHSS评分明显降低,而FMA评分明显升高（P＜0.05）,且治疗组评分明显好于对照组（P＜0.05）。治疗后,两组患者血清炎性因子IL-6、Hcy水平明显降低（P＜0.05）,且治疗组明显低于对照组（P＜0.05）。治疗后,治疗组不良反应总发生率（5.56%）明显低于对照组（12.96%,P＜0.05）。结论 通塞脉片联合硫酸氢氯吡格雷片治疗急性脑梗死疗效确切,可有效改善临床症状,纠正脑神经损伤状态,并减弱机体炎性反应,增强患者运动功能。     

Beyond efficacy: pharmacokinetic differences between clopidogrel,prasugrel and ticagrelor

Introduction: Clinical nonresponse to clopidogrel has been associated with variability in response. This has led to the development of other P2Y12 receptor inhibitors, such as prasugrel and ticagrelor, with different pharmacokinetic characteristics that influence their pharmacodynamics.

Areas covered: Clopidogrel response variability is attributable to its complex pharmacokinetics and is vulnerable to genetic polymorphisms in genes involved in absorption, metabolism and drug–drug interactions (i.e., proton pump inhibitors). Prasugrel which has a simpler metabolism, leading to greater bioavailability, seems to be less affected by genetic or drug–drug interactions and achieves a greater antiplatelet effect. Ticagrelor is the most novel compound approved with a simpler metabolism. Both prasugrel and ticagrelor reached their antiplatelet effect faster and to a much greater extent than clopidogrel. All these differences observed in kinetics explain, to some degree, the efficacy and safety profile observed in clinical trials for these molecules associated with other antiplatelet agents (aspirin, gpIIb/IIIa inhibitors) and anticoagulants.

Expert opinion: Clopidogrel is still the best standard of care. However, the pharmacokinetic advantages of both prasugrel and ticagrelor allow clinicians to center patient management by selecting the best drug for the appropriate subject.     

硫酸氢氯吡格雷对非ST段抬高急性冠脉综合征患者血清hs-CRP及sCD40L的影响

目的 观察硫酸氢氯吡格雷(波立维,Plavix)对非ST段抬高急性冠脉综合征(NSTE-ACS)患者血清高敏C反应蛋白( hs-CRP)及可溶性CD40配体(sCD40L)的影响.方法 将40例NSTE-ACS患者随机分为两组:常规治疗组20例和氢氯吡格雷治疗组20例(在常规治疗基础上加用氢氯吡格雷,首次顿服300 mg,次日起75 mg/d,连服14d).采用酶联免疫吸附法(ELISA)测定全部患者治疗前、后血清hs-CRP及sCD40L浓度.结果两组患者治疗后,血清hs-CRP、sCD40L浓度均较治疗前显著降低(P＜ 0.05 );氢氯吡格雷治疗组治疗前、后血清hs-CRP、sCD40L降低程度较常规治疗组更为显著(P＜0.05).结论 NSTE-ACS患者在常规治疗基础上加用氢氯吡格雷能明显降低血清hs-CRP、sCD40L浓度,有效减轻动脉粥样硬化炎症反应,降低动脉粥样斑块不稳定性.     

老年冠心病患者氯吡格雷联用钙拮抗剂的疗效观察

目的：观察老年冠心病患者使用氯吡格雷（氯吡格雷）联用钙拮抗剂（CCB）的疗效。方法选取我院2010年1月～2013年5月收治的1142名有完整住院治疗资料和随访记录的老年冠心病患者进行回顾性分析,其中仅服用氯吡格雷进行治疗的患者有512例（A组）,服用氯吡格雷联用钙拮抗剂的患者有630例（B组）,B组患者中,有562例患者服用的是二氢吡啶类CCB,另外68例患者服用的是非二氢吡啶类CCB,通过对比观察其治疗效果。结果A组的发病密度为40.28/1000,B组患者的发病密度42.14/1000,粗RR为0.79[95% CI：（0.49-1.15）],调整后的RR为0.51[95% CI：（0.17-1.43）],两组的全因死亡率（P＞0.05）,差异无统计学意义,两组的终点事件发生率（P＞0.05）,差异无统计学意义。对两组患者进行混杂因素的倾向评分加权对比,服用二氢吡啶类CCB和服用非二氢吡啶类CCB的患者对比,OR=1.83[95% CI：（1.3-3.25）],差异有统计学意义（P＜0.05）。结论老年冠心病患者服用氯吡格雷联用钙拮抗剂进行治疗,不会使缺血性心脑血管事件以及全因死亡率增加,服用氯吡格雷联用二氢吡啶类CCB发生缺血性脑血管事件的机率,比服用氯吡格雷联用非二氢吡啶类CCB要低。     

Clopidogrel and vascular disease prevention

SUMMARY

In this editorial we consider some aspects of the use of clopidogrel in current clinical practice.

Clopidogrel may be especially effective in patients with peripheral arterial disease. However, this impression requires confirmation in appropriately designed trials.

Clopidogrel is a useful, evidence-based, antiplatelet agent.     

Efficacy,safety and acceptability of the new pen needle 34G × 3.5 mm: a crossover randomized non-inferiority trial; AGO 02 study

Objective: Insulin injection aspects, such as fear of injection and pain, directly affect glycemic control, patient adherence and quality of life. Use of thinner and shorter needles could increase acceptance of injections. The aim of the study is to evaluate the non-inferiority of the new 34G?×?3.5?mm needle compared to a 32G?×?4?mm in patients with diabetes treated with insulin.

Methods: This is an open, randomized, two-period crossover, non-inferiority trial. Every treatment period lasted 3 weeks. Patients with type 1 or type 2 diabetes, treated with multiple daily insulin injections, were randomly assigned to receive a 34G?×?3.5?mm or a 32G?×?4?mm pen needle. The primary endpoint was the non-inferiority of the 34G?×?3.5?mm in comparison with the 32G?×?4?mm pen needle in terms of percentage absolute change of blood fructosamine (% |ΔFru|), using a non-inferiority margin of 20%.

Results: Overall 77 patients were randomized and 73 completed the study. Patients characteristics were: 52% male, 80.5% affected by type 1 diabetes, mean age 52 years (±14.6), mean BMI 24.5?kg/m² (±5.6), HbA1c 8% (±1.1) and baseline fructosamine level 350 µmol/l (±84). Mean fructosamine levels increased by 0.56 µmol/l with the 34G needle, while a reduction of 7.29?μmol/l was documented with the 32G needle. The difference between the two groups (7.84?μmol/l) was not statistically significant (p?=?.27). The % |ΔFru| between the two groups was 7.55% (95% CI 5.67–9.44), meeting the non-inferiority criterion. Glycemic variability, expressed as standard deviation of fasting blood glucose and post-prandial glucose, was not different between the two treatment groups (p?=?.63 and p?=?.77, respectively).

Conclusions: The 34G?×?3.5?mm needle was non-inferior to the 32G?×?4?mm needle regarding fructosamine levels and glycemic variability supporting the suitability of the 34G?×?3.5?mm needle for insulin injection in patients with diabetes.

Clinical trial registration: NCT02690467