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1.
PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation. 总被引:6,自引:0,他引:6
Dominick J Angiolillo Antonio Fernandez-Ortiz Esther Bernardo Fernando Alfonso Manel Sabaté Cristina Fernández Chiara Stranieri Elisabetta Trabetti Pier Franco Pignatti Carlos Macaya 《Blood coagulation & fibrinolysis》2004,15(1):89-93
The PlA polymorphism (Leu33Pro) of the platelet glycoprotein (GP) IIIa gene has been suggested to play an important role in coronary thrombosis. In vitro studies have shown differences for this polymorphism in platelet sensitivity towards antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic modulation. The aim of the study was to assess the modulatory effect of the PlA polymorphism on clopidogrel-induced antiplatelet effects in 38 patients undergoing coronary stent implantation receiving a 300 mg clopidogrel loading-dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin expression in platelets stimulated with 2 micromol/l adenosine diphosphate using whole blood flow cytometry. The distribution of the homozygous PlA1/A1 and heterozygous PlA1/A2 genotypes were 74 and 26%, respectively. PlA2 carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05). In conclusion, the Pl polymorphism of the GPIIIa gene modulates platelet reactivity towards clopidogrel front loading in patients undergoing coronary stenting. This suggests the need for individualized antithrombotic regimens to optimally inhibit platelet reactivity. 相似文献
2.
High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. 总被引:17,自引:0,他引:17
Dominick J Angiolillo Antonio Fernández-Ortiz Esther Bernardo Celia Ramírez Manel Sabaté Camino Ba?uelos Rosana Hernández-Antolín Javier Escaned Raul Moreno Fernando Alfonso Carlos Macaya 《European heart journal》2004,25(21):1903-1910
AIM: To assess platelet inhibitory effects, interindividual variability in platelet inhibition as well as response to a 600 mg, compared to a standard 300 mg, clopidogrel loading dose (LD) after coronary stenting METHODS AND RESULTS: Platelet function profiles were assessed in 50 patients undergoing coronary stenting receiving either a 300 mg (n=27) or 600 mg clopidogrel LD. ADP (6 microM) and collagen (6 microg/mL) induced platelet aggregation, as well as ADP (2 microM) induced glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed at baseline and 4, 24, and 48 h following clopidogrel front-loading. A more intense and rapid inhibition of platelet activation (both GP IIb/IIIa activation and P-selectin expression) were achieved using a 600 mg, compared to a 300 mg, LD throughout the entire 48 hours (p<0.001). Although there were no differences in platelet aggregation, overall a 600 mg LD increased the number of clopidogrel responders and this was also achieved earlier compared to a 300 mg LD. A 600 mg LD did not reduce interindividual variability of platelet response. CONCLUSION: The use of a 600 mg clopidogrel LD in patients undergoing coronary stenting optimises platelet inhibitory effects early after intervention and may provide a more effective protection against early thrombotic complications. 相似文献
3.
冠状动脉支架置入术后多形核白细胞活化的相关分子的表达 总被引:2,自引:0,他引:2
目的:探讨冠状动脉支架置入术后多形核白细胞(PMN)活化的相关分子的表达。方法:选择18例不稳定型心绞痛患者,在冠状动脉支架置入前(T0)和置入后30 min、3 h、6 h、12 h、24 h(分别为T1~T5)用ELISA法测定血白细胞介素-8(IL-8)、髓过氧化物酶(MPO)、L-选择素(L-selectin)、超敏C反应蛋白(hs-CRP)浓度。结果:支架组T1~T5各时段的PMN相关分子IL-8、MPO、L-selectin、hs-CRP表达增加,它们分别在支架置入后3 h、30 min、12 h、24 h达高峰,同T0比较差异有统计学意义(P<0.01)。结论:冠状动脉支架置入术后IL-、MPO、L-selectin、hs-CRP表达增加,触发PMN的聚集和局部的炎症反应。 相似文献
4.
急性冠状动脉综合征患者冠状动脉支架术前高负荷量氯吡格雷预治疗近期疗效 总被引:21,自引:0,他引:21
目的对比研究氯吡格雷600 mg与300 mg负荷剂量预治疗的急性冠状动脉(冠脉)综合征(ACS)行冠脉支架术的病人的近期疗效和安全性.方法前瞻性注册研究,试验组为2003年2月至2004年7月间316例ACS行冠脉支架术的病人,术前均予600 mg氯吡格雷负荷量预治疗.对照组为2001年10月至2003年2月间309例相同条件病人,支架术前予300 mg氯吡格雷负荷量.研究主要终点为30天支架内亚急性血栓发生,死亡、心肌梗死和紧急靶血管血运重建的联合终点;次要终点为30天出血事件.结果两组临床、冠脉造影及介入治疗基线特征无显著差别.氯吡格雷600 mg组支架内亚急性血栓发生率显著低于300 mg组(0.0% vs 2.6%,P=0.003),300 mg组亚急性血栓发生率与服负荷剂量距手术时间<6 h显著相关(OR=6.665,95%CI1.017~43.521,P=0.048).600 mg组死亡、心肌梗死和紧急靶血管血运重建联合终点发生率显著低于300 mg组(0.95% vs 3.6%,P=0.027),主要及次要出血事件发生率600 mg组为1.27%,300 mg组为0.97%,差异无统计学意义(P=1.00).结论高负荷剂量(600 mg)氯吡格雷预治疗与常规负荷量(300 mg)相比,可显著改善ACS行冠脉支架术病人的近期疗效,且安全性相似. 相似文献
5.
Hon-Kan Yip Chiung-Jen Wu Cheng-Hsu Yang Hsueh-Wen Chang Chih-Yuan Fang Wei-Chin Hung Chi-Ling Hang 《Circulation journal》2005,69(8):890-895
BACKGROUND: This study tested the hypothesis that serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) significantly reflect serial changes in patients with unstable angina, and thus the serum concentrations of these inflammatory biomarkers may be good candidates for predicting late restenosis after coronary stenting. METHODS AND RESULTS: The circulating concentrations of sCD40L and hs-CRP were prospectively measured (both pre-procedure, and on days 21, 90, and 180 after the procedure) in 77 consecutive patients with unstable angina undergoing coronary stenting. These inflammatory mediators were also evaluated in 30 healthy volunteers. The serum concentrations of sCD40L and hs-CRP were significantly higher pre-procedure in study patients than in normal control subjects (all p values < 0.0001). These inflammatory markers then declined to a substantially lower concentration by day 21 (all p values < 0.05). Circulating concentrations of hs-CRP in each patient then differed little from each other afterwards. However, the sCD40L concentration was once again raised significantly on days 90 and 180 as compared to day 21 (both p values < 0.05). This study found no significant link between raised circulating concentrations of sCD40L and hs-CRP and late restenosis. CONCLUSIONS: Circulating concentrations of sCD40L and hs-CRP were significantly increased in unstable angina patients pre-procedure and declined substantially thereafter. However, the circulating concentrations of these 2 inflammatory mediators were not useful in predicting late restenosis following coronary stenting. 相似文献
6.
Daniel Soffer Issam Moussa Kishore J Harjai Judith A Boura Simon R Dixon Cindy L Grines William W O'Neill Gary S Roubin Jeffrey W Moses 《Catheterization and cardiovascular interventions》2003,59(1):21-25
Pretreatment with thienopyridines has been shown to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We determine the impact of angina class on inhibition of platelet aggregation (IPA) following clopidogrel loading. Seventy-two patients (mean age, 64 +/- 11 years; 76% male) were pretreated with 450 mg of clopidogrel at least 3 hr prior to PCI. All patients received ASA 325 mg prior to the procedure. Patients were classified into two groups according to angina class: group 1 = stable angina or Braunwald class 1 unstable angina (UA; n = 33); group 2 = Braunwald class 2 or 3 UA (n = 39). IPA was measured prior to PCI, with the Ichor point-of-care platelet analyzer (Helena Laboratories, Beaumont, TX), using 20 microM of ADP. Group 2 patients were more likely to have prior MI (54% vs. 27%; P = 0.023), prior CABG (33% vs. 5%; P = 0.046), and received IV heparin (64% vs. 27%; P = 0.0018). Mean IPA was significantly lower in group 2 compared to group 1 (19% +/- 22% vs. 32% +/- 22%; P = 0.004). In multivariate analysis, higher angina class was independently associated with lower IPA (P = 0.018). Patients with UA undergoing PCI have a lower IPA following clopidogrel loading with 450 mg. This may indicate the possibility of clopidogrel resistance in such patients. 相似文献
7.
目的 :观察氯吡格雷对不稳定型心绞痛 (UAP)患者血小板功能的影响 ,探讨其临床应用价值。方法 :UAP患者 85例 ,随机分为氯吡格雷负荷剂量组 (n=30 ) ,氯吡格雷常规剂量组 (n=30 )及噻氯匹定治疗组 (n=2 5 )。所有患者在给予阿司匹林 30 0 mg/ d的基础上 ,氯吡格雷负荷剂量组 1次性给予氯吡格雷 (波立维 ) 30 0 mg,氯吡格雷常规剂量组给予波立维 75 mg/ d,噻氯匹定组给予噻氯匹定 (抵克力得 ) 2 5 0 mg/ d,观察 3组患者治疗前 ,氯吡格雷负荷剂量组给药 2 h后 ,氯吡格雷常规剂量组及噻氯匹定组给药 3d后患者血浆 GMP- 14 0含量及血小板最大聚集率(MPAR)的变化。结果 :各组患者治疗后血浆 GMP- 14 0含量及 MPAR较治疗前显著降低 (P<0 .0 1) ,组间血浆GMP- 14 0含量及 MPAR无显著性差异 (P>0 .0 5 )。结论 :氯吡格雷起效迅速 ,首剂负荷剂量 30 0 mg服药后 2 h即可有效抑制血小板激活 ,可达到服用常规剂量氯吡格雷或噻氯匹定连续 3d抑制血小板激活的效果 相似文献
8.
国产和进口氯吡格雷对不稳定性心绞痛患者血小板功能的影响 总被引:9,自引:0,他引:9
目的 观察国产氯吡格雷和进口氯吡格雷对不稳定性心绞痛 (UAP)患者血小板功能的影响 ,比较两药抗血小板作用的优劣及其安全性。方法 4 0例UAP患者随机分为 2组 ,其中国产氯吡格雷组 2 0例 ,进口氯吡格雷组 2 0例。另选健康对照组 10例。两治疗组分别于服用氯吡格雷前、服用氯吡格雷 30 0mg 2h后及服用氯吡格雷 75mg1次 d 1周后抽血查血小板聚集率及血小板活化指标。结果 UAP患者血小板聚集率及血小板活化状态较健康对照组明显增高。治疗前国产和进口氯吡格雷组的血小板聚集率及血小板活化指标无显著差异。治疗后两治疗组之间无显著差异。结论 血小板的活化在UAP的发生、发展过程中起着重要的作用。国产和进口氯吡格雷均有良好的抗血小板作用 ,两者抗血小板聚集和活化的作用相似 ,且无明显的不良反应。 相似文献
9.
Biondi-Zoccai GG Agostoni P Testa L Abbate A Parisi Q Burzotta F Trani C Mongiardo R Vassanelli C Biasucci LM 《Minerva cardioangiologica》2004,52(3):195-208
AIM: Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its hematologic safety, but its efficacy in comparison to ticlopidine is debated. We thus systematically reviewed randomized trials comparing clopidogrel vs ticlopidine after coronary stenting. METHODS: Medline (1/1986-10/2003), BioMed Central, Central, Current Contents, LILACS and mRCT were searched. Fixed-effect relative risks (RR [95% CI]) were computed, and the primary end-point was death. Heterogeneity tests and subgroup analyses were performed according to loading vs non-loading clopidogrel scheme. RESULTS: Five trials were retrieved (2 962 patients, average follow-up 7.4 months). In 3 studies both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (p for heterogeneity=0.12) showed a non-significant trend toward increased mortality in patients treated with clopidogrel (38/1 649 [2.3%]) vs ticlopidine (22/1 313 [1.7%], RR=1.64 [0.94-2.86], p=0.080). After stratification, clopidogrel with loading was associated with non-significantly lower mortality rates than ticlopidine (9/959 [0.9%] vs 13/798 [1.6%], RR=0.68 [0.29-1.63], p=0.39). Instead, clopidogrel without any loading yielded a highly significantly 3-fold increased risk of death than ticlopidine (29/690 [4.2%] vs 9/515 [1.7%], RR=2.9 [1.45-6.1], p=0.0029). Similar results were obtained for the rate of death or non-fatal myocardial infarction. CONCLUSION: This meta-analysis suggests that clopidogrel treatment including a loading regimen is equivalent or may even be superior to ticlopidine after coronary stenting. However, current evidence shows conversely that clopidogrel therapy in the absence of a loading dose is associated with a significantly higher risk of death or myocardial infarction. 相似文献
10.
Enrico Lupia Ornella Bosco Serena Bergerone Anna Erna Dondi Alberto Goffi Elena Oliaro Marco Cordero Lorenzo Del Sorbo Giampaolo Trevi Giuseppe Montrucchio 《Journal of the American College of Cardiology》2006,48(11):2195-2203
OBJECTIVES: We sought to investigate the potential role of elevated levels of thrombopoietin (TPO) in platelet activation during unstable angina (UA). BACKGROUND: Thrombopoietin is a humoral growth factor that does not induce platelet aggregation per se, but primes platelet activation in response to several agonists. No data concerning its contribution to platelet function abnormalities described in patients with UA are available. METHODS: We studied 15 patients with UA and, as controls, 15 patients with stable angina (SA) and 15 healthy subjects. We measured TPO and C-reactive protein (CRP), as well as monocyte-platelet binding and the platelet expression of P-selectin and of the TPO receptor, c-Mpl. The priming activity of patient or control plasma on platelet aggregation and monocyte-platelet binding and the role of TPO in this effect also were studied. RESULTS: Patients with UA showed higher circulating TPO levels, as well as increased monocyte-platelet binding, platelet P-selectin expression, and CRP levels, than those with SA and healthy control subjects. The UA patients also showed reduced platelet expression of the TPO receptor, c-Mpl. In vitro, the plasma from UA patients, but not from SA patients or healthy controls, primed platelet aggregation and monocyte-platelet binding, which were both reduced when an inhibitor of TPO was used. CONCLUSIONS: Thrombopoietin may enhance platelet activation in the early phases of UA, potentially participating in the pathogenesis of acute coronary syndromes. 相似文献
11.
Biochemical evidence of platelet activation in patients with persistent unstable angina 总被引:2,自引:0,他引:2
C W Hamm R L Lorenz W Bleifeld W Kupper W Wober P C Weber 《Journal of the American College of Cardiology》1987,10(5):998-1006
Thromboxane released from activated platelets and prostacyclin of the vessel wall may act as potent antagonistic modulators of platelet aggregability and coronary vascular tone. Therefore, urinary excretion of their major metabolites, 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1 alpha, was studied in 16 patients presenting with prolonged angina at rest. The 10 patients whose condition did not improve under vigorous antianginal treatment within 48 hours exhibited higher thromboxane metabolite excretion than did the 6 patients who responded to therapy (2,208 +/- 1,542 versus 609 +/- 312 ng/g creatinine; p less than 0.001). Elevated values were also found in four of eight patients with sustained postinfarction angina. Enhanced thromboxane metabolite excretion was frequently associated with angiographic evidence of thrombus formation. When nine patients were restudied in a stable phase after 11 +/- 5 months, thromboxane metabolite excretion was consistently normal or high normal. Excretion of prostacyclin metabolites was not depressed in any patient but correlated weakly with thromboxane (r = 0.41). Thus, enhanced thromboxane production as an index of platelet activation may identify patients with active thrombus formation who could benefit most from platelet inhibitory treatment. 相似文献
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We investigated serial changes of circulation platelet activation markers in 40 patients undergoing carotid artery stenting under the protection of dual antiplatelet therapy and filter devices. Monocyte-platelet aggregates and PAC-1 (a marker specific for activated glycoprotein IIb/IIIa) analyzed by flow cytometry were determined in patients with symptomatic stenosis undergoing elective carotid artery stenting. Blood samples were obtained immediately before stent implantation and 0.5 hours, 18 hours, and 6 days after the procedure, respectively. All patients were already on dual antiplatelet therapy of aspirin and clopidogrel before carotid artery stenting, and all were stented with embolic protection devices. Both circulation monocyte-platelet aggregates and PAC-1 did not change significantly at the various time points after the procedure. Serial changes of monocyte-platelet aggregates and PAC-1 analyzed by flow cytometry fail to indicate the occurrence of platelet activation after carotid artery stenting under the treatment with dual antiplatelet therapy before carotid artery stenting and the application of embolic protection devices during the procedure. 相似文献
15.
Impact of clopidogrel on suppression of circulating levels of soluble CD40 ligand in patients with unstable angina undergoing coronary stenting 总被引:1,自引:0,他引:1
Yip HK Chang LT Sun CK Yang CH Hung WC Cheng CI Chua S Yeh KH Wu CJ Fu M 《The American journal of cardiology》2006,97(2):192-194
This study investigated whether a regimen that comprised a loading dose of 300 mg of clopidogrel followed by 75 mg/day could significantly suppress circulating levels of soluble CD40 ligand (sCD40L) in patients who had unstable angina and underwent coronary stenting. Study results showed that the clopidogrel loading dose substantially decreased the circulating level of sCD40L at 24 hours after stenting (p <0.0001). Combined with aspirin, 75 mg/day of clopidogrel continuously decreased sCD40L levels after coronary stenting. 相似文献
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目的探讨在限制性心肌病(RCM)患者中血浆B型利尿肽(BNP)的影响因素。方法入选20例经过组织活检确诊为RCM的患者。将临床、超声心动图和右心导管指标与血浆BNP水平进行相关性分析。结果 RCM患者血浆BNP水平为(792.3±1045.9)ng/L。相关性分析显示BNP与年龄、性别、心功能分级和药物治疗无显著相关;而与超声心动图左心室舒张功能指标,即二尖瓣血流峰值速度E/A比值(r=0.46)、二尖瓣E峰减速时间(r=-0.59)、等容舒张时间(r=-0.45)、组织多普勒成像二尖瓣环舒张早期速度(E′)峰值(r=-0.45)和E/E′比值(r=0.86)有显著相关性(P〈0.05)。BNP与右心导管测定的右心房压力(r=0.45)、右心室舒张末压力(r=0.56)和肺动脉楔压(r=0.46)显著相关(P〈0.05)。多因素回归分析显示二尖瓣E/E′是BNP唯一的独立相关因素(β=0.69,P〈0.05)。结论 RCM患者血浆BNP水平升高,而且与多普勒超声心动图的左心室舒张功能指标以及右心导管测定的右心室舒张压力显著相关。 相似文献
18.
Clinical relevance of homocysteine levels in patients receiving coronary stenting for unstable angina. 总被引:9,自引:0,他引:9
Paolo Ortolani Antonio Marzocchi Cinzia Marrozzini Tullio Palmerini Matteo Aquilina Leonardo Corlianò Francesco Saia Nevio Taglieri Paolo Sbarzaglia Maria Letizia Bacchi Reggiani Angelo Branzi 《Italian heart journal》2004,5(3):189-196
BACKGROUND: We prospectively investigated whether plasma homocysteine (HCY) concentrations are related to target lesion revascularization (TLR) rates in patients with unstable angina undergoing stenting. METHODS: We enrolled 196 consecutive patients with at least one successful coronary stent implantation for unstable angina. RESULTS: The mean vessel diameter was 3.1 +/- 0.5 mm. At follow-up (17.8 +/- 7.5 months), patients with higher HCY levels (> 17 micromol/l, 4th quartile) had similar TLR rates to the rest of the sample (11.1 vs 13.2%, p = 0.90). On the other hand, high HCY levels did seem to be associated with higher total (13.3 vs 0.7%, p = 0.001) and cardiac (6.7 vs 0%, p = 0.01) mortality rates. At multivariate analysis, only target vessel diameter independently predicted TLR, while both HCY levels and target vessel size predicted late total mortality. CONCLUSIONS: At least in patients with a mean vessel diameter > 3 mm, HCY levels cannot be taken as a prognostic indicator of in-stent restenosis for patients with unstable angina. However, in spite of successful percutaneous revascularization, HCY values do seem to strongly influence late mortality. 相似文献
19.
Jure Samardzic Miroslav Krpan Bosko Skoric Marijan Pasalic Mate Petricevic Davor Milicic 《Journal of thrombosis and thrombolysis》2014,38(4):459-469
High on-treatment platelet reactivity (HTPR) on clopidogrel correlates with adverse outcomes in patients treated with percutaneous coronary intervention (PCI). Whether HTPR is a modifiable risk factor for future events is not clear. We evaluated the effect of serial clopidogrel dose adjustment based on platelet function testing (PFT) during 12 months of dual antiplatelet therapy (DAPT) using Multiplate® analyzer in patients with HTPR after PCI in acute coronary syndrome on clinical outcome. Eighty-seven patients were randomized to interventional (n = 43) and control group (n = 44). Blood samples for PFT were drawn at day 1, 2, 3, 7, 30 and at month 2, 3, 6, 9 and 12. Clopidogrel dose was modified at each point of PFT in the interventional group with patients taking up to two additional 600 mg loading doses and a range of 75–300 mg maintenance dose to achieve and maintain optimal platelet reactivity (19–46 U). The incidence of the primary endpoint (composite of cardiovascular death, non-fatal myocardial infarction, target vessel revascularization and ischemic stroke) was significantly higher in the control group (36.3 vs 16.2 %; p = 0.034). There were no differences in total bleeding events (6.8 vs 4.6 %, p = ns). Patients in the interventional group maintained better P2Y12 inhibition during follow-up. We hypothesize that targeting the therapeutic window of platelet reactivity continuously throughout DAPT by dose adjustment of P2Y12 inhibitor may lead to better platelet reactivity control, and thus reduce the rate of ischemic complications in this high risk group of patients. 相似文献