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1.
对2010年Mdeline收载的关于质子泵抑制剂(PPIs)与氯吡格雷相互作用的研究文献进行综述分析,PPIs对氯吡格雷抗血小板聚集活性的影响与多个因素相关:氯吡格雷和阿司匹林合用时,PPIs与氯吡格雷之间无临床意义的药物相互作用;当单用氯吡格雷抗血小板聚集时,PPIs对其药效的影响显著,而且不同的PPIs之间的作用强度有差异;以微观指标(如ADP或花生四烯酸诱导的血小板聚集度)为标准,则氯吡格雷和PPIs之间存在不良药物相互作用,但以宏观指标(如一级事件发生率)为标准则无临床意义的不良药物相互作用;PPIs对氯吡格雷的影响与CYP2C19基因多态性有关:快代谢型患者PPIs对氯吡格雷的抗血小板聚集作用影响显著,慢代谢型无明显影响;与单用氯吡格雷相比,PPI+阿司匹林可以显著降低胃肠道出血事件,对心血管系统没有不良影响。因此,对于PCI术后短期内行氯吡格雷和阿司匹林双抗血小板聚集患者,临床可以根据情况选择任何一个PPIs;对于单用氯吡格雷抗血小板聚集的患者,应该首选与泮托拉唑合用;PPIs合用阿司匹林能有效抗血小板聚集,而且显著减少胃肠道出血事件,因此在必须应用PPIs的情况下,阿司匹林是氯吡格雷的一个有效替代药物。 相似文献
2.
Clopidogrel is a prodrug which requires cytochrome P450 2C19 (CYP 2C19) enzyme for its conversion to an active thiol metabolite. Proton pump inhibitors (PPIs) inhibits enzyme CYP 2C19 interfering with the conversion of clopidogrel into its active metabolite. Studies document the possible interaction of clopidogrel and PPIs leading to a decrease in the antiplatelet efficacy of clopidogrel. A PubMed/MEDLINE database literature search was carried out and the bibliographies of found articles were checked for other relevant literature. Most retrospective cohort studies and studies using platelet markers found a significant association between PPI use especially omeprazole and decreased efficacy of clopidogrel while few comparative trials using clinical outcomes found no association between the same. Pantoprazole was not associated with the decrease in the antiplatelet efficacy of clopidogrel. Patients on dual antiplatelet therapy and/or with a history of gastrointestinal bleed will require gastroprotection in the form of PPIs. In such cases, pantoprazole should be the preferred PPI. Rabeprazole can be used as an alternative. 相似文献
3.
Platelet activation and aggregation have been established as pivotal elements in the pathogenesis of atherosclerotic and ischemic diseases, including acute coronary syndromes. The difficulty of achieving optimal platelet inhibition remains a major constraint following dual-antiplatelet therapy, which can lead to a diminished response following initiation of clopidogrel therapy. Though the absolute mechanisms underlying clopidogrel resistance are controversial, a variety of responsible factors are recognized. Clopidogrel, being a prodrug, requires conversion to an active metabolite for its activity. This metabolism involves various cytochrome P450 (CYP) enzymes at different steps, and it is hypothesized that competitive inhibition of CYPs may contribute to clopidogrel resistance. Proton pump inhibitors (PPIs) are competitive inhibitors of CYPs that can attenuate the antiplatelet activity of clopidogrel, and this can lead to clopidogrel resistance. Available data from different clinical studies have postulated the possibility of a drug-drug interaction between clopidogrel and PPIs. PPIs differ somewhat in their pharmacokinetic properties like bioavaibility and affinity for CYP2C19. However it is not clear whether the proposed drug interaction of PPI with clopidogrel is same with all PPIs (i.e., a class effect) or it is limited to a subset of PPIs (i.e., a drug effect). This interaction needs further assessment with well designed prospective clinical trials, before any change in clinical practice should be considered. In this review, we attempt to evaluate the available evidence exploring drug interactions with PPIs as the underlying mechanism for the reduced antiplatelet effect of clopidogrel. 相似文献
4.
Aspirin and clopidogrel are well-known antiplatelet agents that are widely used across the spectrum of cardio- and cerebrovascular disease. Upper gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, many patients are also treated with a proton pump inhibitor (PPI). PPIs exert gastroprotection by raising intragastric pH. In recent years, it has been heavily discussed whether PPIs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Initially, pharmacodynamic and pharmacokinetic studies suggested a considerable drug interaction between PPIs and clopidogrel, and subsequent clinical studies were conducted to evaluate the clinical impact of this interaction. More recently, it has been reported that PPIs may also attenuate the antiplatelet effect of aspirin. This is particularly interesting, because a fixed combination of aspirin and a PPI (esomeprazole) has been developed and is currently under approval. Given the large number of patients taking aspirin and PPIs, even a small attenuation of the antiplatelet effect of aspirin may have substantial clinical impact. The present editorial summarizes current evidence on this drug interaction and discusses potential clinical implications. 相似文献
5.
INTRODUCTION: There is considerable debate surrounding the clinical relevance of an adverse interaction between clopidogrel and proton pump inhibitors (PPIs). Some studies have indicated that PPIs may attenuate the antiplatelet efficacy of clopidogrel, thus leading to increased risk of thrombotic cardiovascular events. AREAS COVERED: From a literature search of MEDLINE and EMBASE, the authors critically appraised data from systematic reviews, randomised controlled trials and observational studies that evaluated platelet function and clinical outcomes in patients receiving concomitant clopidogrel and PPIs. EXPERT OPINION: The evidence from platelet function and cardiovascular outcome studies is highly inconsistent. Higher quality data from randomised trials indicate that use of PPI therapy for up to 6 months is unlikely to cause any adverse interaction with clopidogrel, and there are gastrointestinal benefits with PPI use. 相似文献
6.
The American Heart Association/American College of Cardiology guidelines recommend initiating a proton-pump inhibitor (PPI) to prevent gastrointestinal bleeding if patients are receiving concomitant therapy with clopidogrel and aspirin. Recently, concern has been raised regarding the ability of PPIs to decrease the antiplatelet activity of clopidogrel. To date, there are 16 studies that evaluated the outcomes of using clopidogrel with a PPI. One of the studies has shown that adding lansoprazole to clopidogrel has no effect on the concentration of clopidogrel's inactive metabolite. The eight clinical trials that studied the effect of using PPIs and clopidogrel together on platelet function testing have shown differing effects between PPIs. Concurrent omeprazole and clopidogrel use was shown to decrease the antiplatelet effects of clopidogrel in three studies; whereas pantoprazole, lansoprazole and esomeprazole have been shown to have no significant effect on the antiplatelet response to clopidogrel. Six other studies showed that using PPIs and clopidogrel together led to adverse clinical outcomes; however, one study that did a separate analysis on pantoprazole, showed that using pantoprazole with clopidogrel had no significant impact on clinical outcomes. Post hoc analysis from a large randomized trial comparing prasugrel with clopidogrel indicated no clinically significant effects of PPIs in patients treated with either prasugrel or clopidogrel. Preliminary results from a prospective, randomized trial comparing cardiovascular clinical outcomes between omeprazole and placebo in clopidogrel-treated patients have been reported and suggest no interaction. However, the study was stopped prematurely secondary to loss of funding and follow-up limited to a median of 133 days so no firm conclusions were drawn. The data currently available regarding concurrent clopidogrel and PPI use are limited, so further studies are needed to provide a definite conclusion. Until additional prospective studies are available, the use of clopidogrel with a PPI should be avoided, if possible, and a H(2)-receptor antagonist be selected instead. Prasugrel may be administered safely with a PPI as there is currently no evidence of a pharmacokinetic, pharmacodynamic or adverse clinical effects. 相似文献
7.
P2Y12受体拮抗剂是一类作用于血小板P2Y12受体、抑制血小板聚集的药物,临床上主要用于预防和治疗心血管疾病的血栓事件。氯吡格雷是目前临床上首选的双重抗血小板药物之一,但其疗效受限于CYP2C19基因的多态性、与质子泵抑制剂(PPIs)的相互作用和起效缓慢等。目前,一些新型P2Y12受体拮抗剂类抗血小板药物(如普拉格雷、替卡格雷等)已经进入临床,几项大型临床试验对其疗效和安全性进行了评价。本文对比了新型P2Y12受体拮抗剂与氯吡格雷在药理学、药代动力学、有效性和安全性方面的差异,并探讨其临床应用,为临床合理用药提供参考。 相似文献
8.
Yasu T Ikee R Miyasaka Y Chubachi H Saito S 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》2010,130(12):1743-1750
After coronary stent implantation, dual-antiplatelet therapy (DAT), such as aspirin and clopidogrel, is essential to prevent stent thrombosis. Proton-pump inhibitors (PPIs) may be used to prevent gastrointestinal (GI) bleeding during DAT, but there is no evidence for the efficacy of PPIs in this setting. Because both clopidogrel and PPIs are metabolized by cytochrome P450 (CYP) 2C19, there is a possibility that, through drug interaction, PPIs diminish the antiplatelet effect of clopidogrel. In this retrospective cohort study, we evaluated the efficacy and safety of rabeprazole in patients receiving DAT of clopidogrel and aspirin after drug-eluting stent implantation. In 199 patients treated with DAT alone (control group) and 103 patients treated with rabeprazole plus DAT (rabeprazole group), we examined the incidences of GI bleeding and major adverse cardiac events (MACE) including stent thrombosis. The incidence of GI bleeding was not significantly different between the groups (hazard ratio 0.47 [95% confidence interval 0.15-1.42], P=0.18; P=0.17 in log-rank test), although no patient with severe bleeding was observed in the rabeprazole group. The use of rabeprazole did not increase the incidence of MACE (hazard ratio 1.28 [95% confidence interval 0.54-3.00], P=0.56; P=0.56 in log-rank test). One patient who developed subacute stent thrombosis under DAT was genetically proven to be a CYP2C19 poor metabolizer. The effect of rabeprazole to prevent GI bleeding is limited in patients receiving DAT. It remains to be confirmed whether these results may depend on CYP2C19 polymorphisms or a class of PPIs. 相似文献
9.
《Expert review of clinical pharmacology》2013,6(1):89-102
The American Heart Association/American College of Cardiology guidelines recommend initiating a proton-pump inhibitor (PPI) to prevent gastrointestinal bleeding if patients are receiving concomitant therapy with clopidogrel and aspirin. Recently, concern has been raised regarding the ability of PPIs to decrease the antiplatelet activity of clopidogrel. To date, there are 16 studies that evaluated the outcomes of using clopidogrel with a PPI. One of the studies has shown that adding lansoprazole to clopidogrel has no effect on the concentration of clopidogrel’s inactive metabolite. The eight clinical trials that studied the effect of using PPIs and clopidogrel together on platelet function testing have shown differing effects between PPIs. Concurrent omeprazole and clopidogrel use was shown to decrease the antiplatelet effects of clopidogrel in three studies; whereas pantoprazole, lansoprazole and esomeprazole have been shown to have no significant effect on the antiplatelet response to clopidogrel. Six other studies showed that using PPIs and clopidogrel together led to adverse clinical outcomes; however, one study that did a separate analysis on pantoprazole, showed that using pantoprazole with clopidogrel had no significant impact on clinical outcomes. Post hoc analysis from a large randomized trial comparing prasugrel with clopidogrel indicated no clinically significant effects of PPIs in patients treated with either prasugrel or clopidogrel. Preliminary results from a prospective, randomized trial comparing cardiovascular clinical outcomes between omeprazole and placebo in clopidogrel-treated patients have been reported and suggest no interaction. However, the study was stopped prematurely secondary to loss of funding and follow-up limited to a median of 133 days so no firm conclusions were drawn. The data currently available regarding concurrent clopidogrel and PPI use are limited, so further studies are needed to provide a definite conclusion. Until additional prospective studies are available, the use of clopidogrel with a PPI should be avoided, if possible, and a H2-receptor antagonist be selected instead. Prasugrel may be administered safely with a PPI as there is currently no evidence of a pharmacokinetic, pharmacodynamic or adverse clinical effects. 相似文献
10.
近年来,临床研究发现氯吡格雷合用质子泵抑制剂(proton pump inhibitors,PPI)可能会增加急性冠脉综合征(acute coronary syndrome,ACS)或经皮冠状动脉介入(percutaneous coronary intervention,PCI)术后患者心血管不良事件发生的风险,因此,联合用药存在争议。本文从氯吡格雷与CYP2C19多态性、PPI与氯吡格雷在药理及临床作用上的相互影响、相关临床研究来深入解析药物相互作用。药代动力学研究的Meta分析结果显示,PPI可能削弱了氯吡格雷抗血小板的效应。10个临床观察性研究都体现了这个观点,但文献质量偏低,而其余3篇低质量的观察性研究、5篇中等质量的观察性研究和1篇高质量的RCT均未发现氯吡格雷合用PPI会显著增加患者心血管不良事件的发生风险。 相似文献
11.
Teng R 《Clinical pharmacokinetics》2012,51(5):305-318
Acute coronary syndromes (ACS) remain life-threatening disorders associated with high morbidity and mortality, despite advances in treatment over the last decade. Adenosine diphosphate-induced platelet activation via P2Y(12) receptors plays a pivotal role in the pathophysiology of ACS. The current standard of treatment involves dual antiplatelet therapy with aspirin (acetylsalicylic acid) and the thienopyridine clopidogrel. Numerous studies and wide use in clinical practice have established the value of this approach in the treatment of ACS. However, clopidogrel treatment has a number of limitations, including a delayed onset of action due to the need for metabolic activation, variable and reduced antiplatelet effects in patients with certain genotypes, and prolonged recovery of platelet function due to irreversible P2Y(12) receptor binding. Prasugrel, a new thienopyridine, has demonstrated more consistent inhibition of platelet aggregation (IPA) than clopidogrel, although this thienopyridine also requires metabolic activation and treatment is associated with a significantly increased risk of life-threatening and fatal bleeding. The recently approved oral antiplatelet agent ticagrelor has the potential to overcome some of the limitations of current therapy due to its unique pharmacokinetic and pharmacodynamic profiles. It is a member of a new chemical class, the cyclopentyltriazolopyrimidines, and is a potent P2Y(12) receptor antagonist. Ticagrelor is rapidly absorbed, with a median time to maximum concentration of 1.3-2.0 hours. Ticagrelor does not require metabolic activation to an active form and binds rapidly and reversibly to the P2Y(12) receptor. As well as exerting effects via platelet P2Y(12) receptors, ticagrelor may confer additional benefits via inhibition of non-platelet P2Y(12) receptors. The pharmacokinetic profile of ticagrelor is not significantly affected by age, gender or administration with food, nor by prior treatment with, or responsiveness to, clopidogrel. Ticagrelor is primarily metabolized via the cytochrome P450 (CYP) 3A4 enzyme, rapidly produces plasma concentration-dependent IPA that is greater and more consistent than that observed with clopidogrel, and can also enhance platelet inhibition and overcome non-responsiveness in patients previously treated with clopidogrel. Importantly, the pharmacodynamic characteristics of ticagrelor are not influenced by CYP2C19 and ABCB1 genotypes. This article summarizes our current knowledge regarding the pharmacokinetic, pharmacodynamic and pharmacogenetic profile of ticagrelor. 相似文献
12.
氯吡格雷能够降低冠心病患者再次发生心肌梗死的风险,故广泛用于急性冠脉综合征和经皮冠脉介入术后的患者。临床相关指南建议,氯吡格雷应与质子泵抑制剂(proton pump inhibitor,PPI)合用以减少氯吡格雷的胃肠道不良反应。但是,氯吡格雷需经肝脏细胞色素P450酶的同功酶CYP2C19代谢才能转化为活性产物发挥作用,而PPI同样主要由CYP2C19代谢。药代动力学研究显示,氯吡格雷与奥美拉唑合用会发生药物相互作用、由此降低氯吡格雷的抗血小板作用,而泮托拉唑与氯吡格雷的相互作用不明显。发表于2009年的系列回顾性病例对照研究表明,氯吡格雷与PPI合用会增加心血管不良事件的发生风险。但这一研究结果并未得到前瞻性的随机、对照研究和荟萃分析的证实。因此,目前仍需进行大规模的前瞻性的随机、对照试验来分析氯吡格雷和PPI合用与心血管不良事件风险间的相关性。鉴于临床上有大量服用氯吡格雷的患者需合用PPI来降低胃肠道出血风险,建议现最好选用与氯吡格雷相互作用较小的泮托拉唑。 相似文献
13.
Cameron D. Thomas Alexis K. Williams Craig R. Lee Larisa H. Cavallari 《Pharmacotherapy》2023,43(2):158-175
Oral P2Y12 inhibitors are commonly prescribed for cardiovascular disease and include clopidogrel, prasugrel, and ticagrelor. Each of these drugs has its strengths and weaknesses. Prasugrel and ticagrelor are more potent inhibitors of platelet aggregation and were shown to be superior to clopidogrel in preventing major adverse cardiovascular events after an acute coronary syndrome and percutaneous coronary intervention (PCI) in the absence of genotyping. However, both are associated with an increased risk for non-coronary artery bypass-related bleeding. Clopidogrel is a prodrug requiring bioactivation, primarily via the CYP2C19 enzyme. Approximately 30% of individuals have a CYP2C19 no function allele and decreased or no CYP2C19 enzyme activity. Clopidogrel-treated carriers of a CYP2C19 no function allele have decreased exposure to the clopidogrel active metabolite and lesser inhibition of platelet aggregation, which likely contributed to reduced clopidogrel efficacy in clinical trials. The pharmacogenetic data for clopidogrel are most robust in the setting of PCI, but evidence is accumulating for other indications. Guidance is available from expert consensus groups and regulatory agencies to assist with integrating genetic information into P2Y12 inhibitor prescribing decisions, and CYP2C19 genotype-guided antiplatelet therapy after PCI is one of the most common examples of clinical pharmacogenetic implementation. Herein, we review the evidence for pharmacogenetic associations with clopidogrel response and outcomes with genotype-guided P2Y12 inhibitor selection and describe guidance to assist with pharmacogenetic implementation. We also describe processes for applying genotype data for P2Y12 inhibitor therapy selection and remaining gaps in the field. Ultimately, consideration of both clinical and genetic factors may guide selection of P2Y12 inhibitor therapy that optimally balances the atherothrombotic and bleeding risks. 相似文献
14.
Over the last two decades or more, anti-platelet therapy has become established as a cornerstone in the treatment of patients with ischaemic cardiovascular disease, since such drugs effectively reduce arterial thrombotic events. The original agent used in this context was aspirin (acetylsalicylic acid) but, with the advent of adenosine diphosphate (ADP) receptor antagonists, the use of dual anti-platelet therapy has resulted in further improvement in cardiovascular outcomes when compared with aspirin alone. The first group of platelet ADP receptor antagonists to be developed was the thienopyridine class, which comprise inactive pro-drugs that require in vivo metabolism to their active metabolites before exerting their inhibitory effect on the P2Y(12) receptor. Clopidogrel has been the principal ADP receptor antagonist in use over the past decade, but is limited by variability in its in vivo inhibition of platelet aggregation (IPA). The pharmacokinetics of clopidogrel are unpredictable due to their vulnerability to multiple independent factors including genetic polymorphisms. Expression of the 3435T/T genetic variant encoding the MDR1 gene for the P-glycoprotein efflux transporter results in a significantly reduced maximum drug concentration and area under the plasma concentration-time curve as intestinal absorption of clopidogrel is reduced; and the expression of the mutant *2 allele of CYP2C19 results in similar pharmacokinetic effects as the two cytochrome P450 (CYP)-mediated steps required for the production of the active metabolite of clopidogrel are impaired. These variable pharmacokinetics lead to erratic pharmacodynamics and cannot reliably be overcome with increased dosing. Both prasugrel, a third-generation thienopyridine, and ticagrelor, a cyto-pentyl-triazolo-pyrimidine, have more predictable pharmacokinetics and enhanced pharmacodynamics than clopidogrel. Neither appears to be affected by the same genetic polymorphisms as clopidogrel; prasugrel requires only a single CYP-mediated step to produce its active metabolite and ticagrelor is not a pro-drug. Enhanced IPA by both prasugrel and ticagrelor is achieved at the expense of increased major bleeding, although this is partially mitigated in the case of ticagrelor due to its reversible IPA. However, the reversible binding of ticagrelor to the P2Y(12) receptor requires a twice-daily dosing regimen. Due to limited data from clinical studies, the use of prasugrel is currently restricted to individuals undergoing percutaneous coronary intervention who are ≤75 years old and have a body weight ≥60 kg. The clinical data for ticagrelor are more comprehensive and this drug therefore has a place in the management of patients with acute coronary syndrome at moderate-to-high risk of ischaemic events, irrespective of treatment strategy. Here we review in detail the pharmacokinetics and pharmacodynamics of clopidogrel, prasugrel and ticagrelor, and explore the implications of the differences in these parameters for their clinical use. 相似文献
15.
目的观察经皮冠脉内介入术(percutaneous coronary intervention,PCI)后使用西洛他唑对阿司匹林致上消化道出血患者的外周血血小板聚集率、PGE2及心血管事件发生率的影响。方法 64例确诊冠心病并行PCI术后的患者,服用阿司匹林和氯吡格雷双重抗血小板治疗出现阿司匹林相关上消化道出血,其中32例患者改用西洛他唑加氯吡格雷,而另外32例患者出血治疗后继续原抗血小板治疗方案,随访比较两组患者血小板聚集率、PGE2及心血管事件发生率。结果平均随访(0.9±0.1)年,两组患者血小板聚集率均明显下降,西洛他唑组的血小板聚集率显著低于阿司匹林组(P<0.05),外周血PGE2的浓度高于阿司匹林组(P<0.05),但两组患者临床不良事件发生率差异无统计意义。结论对PCI术后上消化道出血患者,应用西洛他唑替代阿司匹林,联用氯吡格雷进行抗血小板治疗,经过短期的临床观察,其血小板聚集率优于阿司匹林,升高外周血PGE2的浓度,且安全性与阿司匹林相当,可用于预防上消化道出血的复发。 相似文献
16.
氯吡格雷是临床上常用的抗血小板药物,它通过不可逆地结合于P2Y12受体血小板上,从而减少了二磷酸腺苷介导的血小板聚集。虽然氯吡格雷疗效显著,但是存在明显的个体差异。了解可能引起氯吡格雷个体差异的因素从而提高氯吡格雷的疗效,降低不良心血管事件的发现,是目前临床工作者关心的问题。本文综述了影响氯吡格雷药动学和药效学的基因多态性,旨为氯吡格雷临床个体化给药提供一定的参考依据。 相似文献
17.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the standard of care in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) because this regimen has markedly decreased the rate of cardiovascular events. The substantial variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. Baseline demographic and clinical variables contributing to the observed variability have been identified. Besides this, research within the past decade has focused on the impact of genetic polymorphisms encoding transport systems or enzymes involved in the absorption and metabolism of these drugs. Loss-of-function polymorphisms in CYP2C19 are the strongest individual variables affecting pharmacokinetics and antiplatelet response to clopidogrel, but explain no more than 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. No genetic variables contributing to clinical outcomes of patients treated with the newer P2Y12 receptor antagonists, prasugrel or ticagrelor, have been identified so far. This review aims to provide an update on the current status of genotype-based personalized therapy with clopidogrel. 相似文献
18.
Platelet activation subsequent to the adhesion of platelets to the vascular wall results in the release of mediators that promote platelet aggregation, which plays a pivotal role in the development of the polyvascular atherosclerotic disease that can be referred to by the acronym 'ATIS' (AtheroThrombosIS). The currently available antiplatelet drugs used to prevent vascular events in patients with cardiovascular disease, including peripheral arterial disease (PAD), include aspirin and thienopyridines such as clopidogrel. These drugs decrease platelet aggregability, each of them by inhibiting a different pathway of platelet activation and recruitment. Aspirin acts by inhibiting thromboxane A2 (TXA2) formation through the inhibition (acetylation) of cyclo-oxygenase. On the other hand, thienopyridines suppress the platelet aggregation adenosine diphosphate (ADP) pathway by inhibiting the platelet P2Y12 subtype of the ADP receptor. The results of the large ATT (Antithrombotic Trialists' Collaboration) meta-analysis of published clinical studies on aspirin, reported in 2002, confirmed the previous meta-analysis and major trials that treatment with aspirin (mixed with other antiplatelet agents in these large meta-analyses) can prevent vascular events in high-risk patients with cardiovascular disease. However, it must be stressed that specifically in PAD patients no significant effect of aspirin was demonstrated in a more recent meta-analysis. This was also the case for primary and secondary prevention in diabetic patients. In keeping with these observations, neither a five-year follow-up study of Japanese diabetic patients in the JPAD (Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes) study, a seven-year follow-up study of UK diabetic patients with PAD in the POPADAD (Prevention of Progression of Arterial Disease and Diabetes) study, nor a very recent Scottish study in the same population of diabetics with PAD revealed a significant beneficial effect for aspirin in preventing ischaemic events. This failure may be a consequence of more rapid recovery of platelet aggregability following each dose of aspirin in these PAD or diabetic populations, with the accelerated platelet turnover resulting in a condition of aspirin resistance. Results of the large scale CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) trial that evaluated clopidogrel in patients with cerebral infarction, myocardial infarction or PAD have found clopidogrel to be significantly more effective than aspirin in preventing ischaemic events in patients with PAD. Furthermore, a subgroup analysis of the study has confirmed the efficacy of clopidogrel in diabetic patients with PAD, showing a significant reduction of events in clopidogrel-treated, compared with aspirin-treated, diabetic patients. These results are also likely to be attributable to the greater frequency of aspirin resistance in aspirin-treated patients in these populations (diabetics and/or PAD). Platelets, through activation and aggregation, have an important role in ATIS. However, although antiplatelet therapy with low-dose aspirin has been reported to prevent vascular events in high-risk patients with cardiovascular disease, recent studies in patients with PAD or diabetes mellitus have failed to support the efficacy of aspirin in preventing vascular events in these patient populations. In contrast, clopidogrel appears to be a useful antiplatelet agent in the prevention of vascular events in patients with PAD or diabetes. 相似文献
19.
Platelets play a crucial role in thrombosis, inflammation, immunity and atherogenesis. Antiplatelet agents are widely used in patients with acute coronary syndrome and other cardiovascular disorders. Aspirin and clopidogrel are the most commonly prescribed antiplatelet agents, with a relatively safe profile and efficiency in a variety of clinical conditions. Numerous prospective studies have revealed variability of antiplatelet efficacy. The so called "antiplatelet resistance" prompted a search for mechanisms implicated in poor responsiveness to aspirin and clopidogrel therapy. In this regard, genetic polymorphisms in the platelet receptor genes attracted considerable interest. Specific genetic variants in platelet receptors such as the P2Y12, glycoprotein (GP) IIb/IIIa, GPIa/IIa, GPIb/IX/V and the cytochrome P450 (CYP) family of genes are associated with variable response to antiplatelet therapy and cardiovascular events. Genetic polymorphisms and haplotypes that comprehensively capture the genetic information encoded within the platelet receptor genes can, to some extent, predict response to the antiplatelet drug better than any single genotype. Genotyping for multiple receptor variants in patients on antiplatelet therapy, complemented by standardized quantification of platelet function, can provide useful information for future drug design studies and possibly for personalized antiplatelet therapy and prevention of thrombotic events. Additional information is, however, needed to evaluate the cost-effectiveness of complex genetic and platelet function testing. 相似文献
20.
Antithrombotic therapy is imperative in the management of patients presenting with an acute coronary syndrome (ACS). The combination of antiplatelet therapy in conjunction with antithrombotic therapy has become the standard of care in improving the morbidity and mortality of patients with an ACS and in reducing ischemic complications of percutaneous coronary intervention. Patients with an ACS are at increased risk for a recurrent event, both in-hospital and for several months afterward. Secondary prevention to reduce these events is accomplished through the establishment of appropriate medical therapy. Dual antiplatelet therapy with aspirin and adenosine 5'-diphosphate P2Y(12) receptor blockers such as ticlopidine or clopidogrel are integral components of this regimen; however, both of these thienopyridines have a relatively slow onset of action and variable bioavailability. Prasugrel, a third-generation thienopyridine approved by the US FDA in 2009, has a more rapid onset of platelet inhibition than clopidogrel and ticlopidine because of increased efficiency of prodrug-to-active metabolite conversion. The result is higher and less variable concentration of the active metabolite within 60 minutes following oral dosing. Phase II and III trials assessing the safety and efficacy of prasugrel have been completed, including JUMBO-TIMI 26, PRINCIPLE-TIMI 44, and TRITON-TIMI 38. These trials demonstrated greater inhibition of platelet aggregation and lower rates of the composite endpoint of death, non-fatal myocardial infarction, and stroke compared with clopidogrel. However, major bleeding occurred more frequently with prasugrel treatment than with clopidogrel. This review highlights the current state of evidence-based antiplatelet therapy and provides guidance on appropriate use of prasugrel in cardiovascular medicine. 相似文献