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1.
Trenk D Hochholzer W Frundi D Stratz C Valina CM Bestehorn HP Büttner HJ Neumann FJ 《Thrombosis and haemostasis》2008,99(1):174-181
Early studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 muM was similar irrespective of statin treatment at baseline (p = 0.968). RPA at CA was 46.2 +/- 16.8% in patients without statin (n = 682), 45.5 +/- 17.0% in patients with atorvastatin (n = 255), 45.8 +/- 16.3% with simvastatin (n = 335), 47.3 +/- 14.9% with fluvastatin (n = 42) and 45.9 +/- 16.2% with pravastatin (n = 81; p = 0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n = 553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p = 0.645). Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI. 相似文献
2.
Clopidogrel (CLP) is a second generation thienopyridine drug commonly used in secondary prevention of ischemic stroke (IS). Its antiplatelet response maybe variable due to genetic and non-genetic factors. Adipokines may affect platelet aggregation through ADP mediated platelet signalling. However, the combined effect of CYP genetic variants and adipokines on antiplatelet response of clopidogrel is unclear. Patients of IS/Transient ischemic attack (TIAs) within 3 months were prospectively screened following clopidogrel treatment. Major exclusions were cardioembolic and non atherosclerotic strokes. Antiplatelet effect of clopidogrel along with adipokine (Leptin and adiponectin) levels and genotyping of CYP, P2Y12 gene were investigated. Rare genetic variants were confirmed by DNA sequencing. 204 patients with ischemic stroke/TIAs were screened and 163 were recruited. 85 (52.1%) patients were poor responders to clopidogrel. Antiplatelet response to clopidogrel was weaker in females [Median 8.0 (IQR: 3.0–14.0)] compared to males [Median 5.0 (IQR: 2.0–10.0)]. In female subgroup analysis, association was found among high leptin levels and PPI (+) usage in poor responders. None of the genetic variants (CYP2C19*2,*3,*4*, CYP2C9*3, CYP2B6 and P2Y12) were found to influence the antiplatelet effects (p > 0.05). On multivariable logistic regression, a poor clopidogrel response was associated with female gender (Adjusted OR 2.55, 95% CI: 1.05–6.18) and PPI usage (Adjusted OR 2.42, 95% CI: 1.09–5.34). Despite a high prevalence of clopidogrel resistance in the North Indian stroke patients, female gender rather than genetic polymorphisms of CYP and P2Y12 genes may influence its antiplatelet effect. Further research may ascertain the role of gender on clopidogrel response. 相似文献
3.
Kreutz RP Breall JA Kreutz Y Owens J Lu D Bolad I von der Lohe E Sinha A Flockhart DA 《Thrombosis research》2012,130(2):198-202
Introduction
Clopidogrel inhibits ADP mediated platelet aggregation through inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces platelet aggregation by binding to protease activated receptor-1 (PAR-1), and inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated platelet aggregation may be dependent on extent of clopidogrel response.Material and Methods
Platelet aggregation was measured in 55 patients undergoing elective PCI at 16-24 hours after 600 mg clopidogrel loading dose by light transmittance aggregometry using ADP 20 μM and thrombin receptor agonist peptide (TRAP) at 15 μM and 25 μM as agonists. Genomic DNA was genotyped for common CYP2C19 variants.Results
Increasing quartiles of 20 μM ADP induced platelet aggregation after clopidogrel loading were associated with increasing levels of TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel non-responders) of post treatment ADP aggregation had significantly higher TRAP mediated aggregation than the patients in the lowest quartile (clopidogrel responders) [TRAP 15 μM: 79.6 ± 5% vs. 69.5 ± 8%, p < 0.001].Conclusions
Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP. Addition of PAR-1 antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation. 相似文献4.
Angiolillo DJ Bernardo E Palazuelos J Desai B Weisberg I Alfonso F Guzman LA Hernández-Antolin R Zenni MZ Macaya C Fernandez-Ortiz A Bass TA 《Thrombosis and haemostasis》2008,99(1):161-168
The currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n = 20) or 150 mg (n = 20) daily maintenance dose of clopidogrel for 30 days; afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 microM and 5 microM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 microM ADP-induced platelet aggregation compared to patients on 75 mg/day (52.1 +/- 9% vs. 64.0 +/- 8%; p < 0.001; primary endpoint). The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p < 0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 microM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI. 相似文献
5.
Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting 总被引:11,自引:0,他引:11
Angiolillo DJ Fernandez-Ortiz A Bernardo E Ramírez C Barrera-Ramirez C Sabaté M Hernández R Moreno R Escaned J Alfonso F Bañuelos C Costa MA Bass TA Macaya C 《Thrombosis research》2005,115(1-2):101-108
BACKGROUND: Although patients undergoing coronary stenting routinely receive dual antiplatelet treatment to reduce the risk of stent thrombosis, this undesired event still occurs. A suboptimal response to clopidogrel treatment (low responders) has been suggested to contribute to stent thrombosis. In the present study, platelet function profiles were assessed in patients undergoing coronary stenting receiving a standard 300-mg clopidogrel loading dose with the aim to identify low clopidogrel responders. MATERIALS AND METHODS: Platelet aggregation was assessed by light transmittance aggregometry following 6 microM ADP stimuli in 48 patients before and 10 min, 4 and 24 h after receiving clopidogrel front-loading. Patients having > or =40% inhibition of platelet aggregation 24 h after clopidogrel administration were defined as normal responders, whereas those having <40% inhibition were low responders. Glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed by whole blood flow cytometry following 2 microM ADP stimuli at the same time points. Platelet function profiles were compared between normal and low clopidogrel responders. RESULTS: Twenty-seven patients (56%) were normal responders and 21 (44%) low responders. Baseline GP IIb/IIIa activation was higher in low responders (74.6+/-16.6% vs. 58.2+/-24.5%, p=0.03). Although GP IIb/IIIa activation reduced following clopidogrel front-loading in both groups, it remained increased among low responders at 24 h (58.6+/-21.3% vs. 40.2+/-28.7%, p=0.05) and during the overall study time course (p=0.02). There were no differences in P-selectin expression. CONCLUSIONS: A considerable proportion of patients have an early suboptimal response to a 300-mg clopidogrel loading dose. An increased GP IIb/IIIa activation before intervention may identify this group of patients suggesting the use of a more aggressive antithrombotic treatment in these individuals. 相似文献
6.
Perneby C Wallén NH Hofman-Bang C Tornvall P Ivert T Li N Hjemdahl P 《Thrombosis and haemostasis》2007,98(6):1316-1322
Stress may counteract responses to antiplatelet drug treatment. We investigated if adding clopidogrel to aspirin treatment could attenutate stress-induced platelet activation and myocardial ischemia in patients with coronary artery disease (CAD). Thirty-one male patients with documented CAD-treated with aspirin (75-160 mg daily) were randomized to co-treatment with clopidogrel (n = 16) or placebo (n = 15). A symptom-limited exercise test and 48-hour (h) Holter monitoring were performed before and after two weeks of double-blind treatment. Platelet function was assessed by flow cytometry and impedance aggregometry in whole blood. Exercise-induced and ambulatory ischemia was assessed from electrocardiographic (ECG) recordings. Clopidogrel treatment inhibited ADP-induced platelet P-selectin expression by 64% (22-87%), and attenuated the P-selectin response to thrombin (p < 0.001), and platelet aggregation induced by low-dose collagen (p < 0.01). Exercise ( approximately 110W) increased heart rate similarly, and caused approximately 1.8 mm ST-segment depression both before and after treatment. Exercise caused platelet activation, i.e. increased circulating activated single platelets and platelet-platelet aggregates, enhanced the in-vitro responsiveness to ADP or thrombin stimulation, and increased platelet-leukocyte aggregation. Clopidogrel inhibited ADP-induced platelet activation to a similar relative degree at rest and during exercise, but did not attenuate the platelet activating effect of exercise. Addition of clopidogrel to aspirin treatment did not attenuate either ambulatory or exercise-induced ischemia. In conclusion, adding clopidogrel to aspirin treatment inhibited platelet activation by both ADP, thrombin and collagen in vitro, but did not influence the prothrombotic responses to exercise. Intensified antiplatelet treatment did not reduce ECG signs of either exercise-induced or ambulatory myocardial ischemia. 相似文献
7.
Asami Kamada Mie Shimizu Kazumasa Oura Makiko Yoshida Keisuke Tsuda Kiyotaka Oi Yoko Ishigaku Tatsunori Natori Shinsuke Narumi Ryo Itabashi Tetsuya Maeda Yasuo Terayama 《Journal of stroke and cerebrovascular diseases》2021,30(3):105547
ObjectivesThe inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA).Materials and MethodsPRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants.ResultsIn healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited.ConclusionsWe showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP. 相似文献
8.
9.
Angiolillo DJ Fernandez-Ortiz A Bernardo E Ramírez C Cavallari U Trabetti E Sabaté M Jimenez-Quevedo P Hernández R Moreno R Escaned J Alfonso F Bañuelos C Costa MA Bass TA Pignatti PF Macaya C 《Thrombosis research》2005,116(6):491-497
INTRODUCTION: Clopidogrel inhibits the ADP subtype P2Y(12) receptor. Recently, polymorphisms of this receptor have been associated with different degrees of platelet aggregation in healthy volunteers and have been suggested to modulate clopidogrel response. However, the role of gene sequence variations of the P2Y(12) receptor in patients treated with clopidogrel has not yet been assessed. MATERIALS AND METHODS: The T744C polymorphism of the P2Y(12) receptor gene was assessed in 119 patients: 36 undergoing coronary stenting receiving a 300 mg loading dose (Group A) and 83 on long-term clopidogrel (75 mg/day) treatment (Group B). Patients were divided into 2 subgroups according to the presence or absence of the C allele: carriers (CT heterozygotes and CC homozygotes) and non-carriers (TT homozygotes). Platelet aggregation, assessed by light transmittance aggregometry following ADP, collagen, TRAP and epinephrine stimuli, and platelet activation (GP IIb/IIIa activation and P-selectin expression), assessed by whole blood flow cytometry in ADP and TRAP-stimulated platelets, were performed. Platelet function was assessed at baseline and 4 and 24 h following clopidogrel loading dose in Group A and when patients where on clopidogrel treatment for at least 1 month in Group B. RESULTS: The genotype distribution of Group A was: 22/36 (61.1%) non-carriers and 14/36 (38.9%) carriers of the C allele; Group B: 57/83 (68.7%) non-carriers and 26/83 (31.3%) carriers of the C allele. There were no differences between groups for all the assessed platelet function assays. CONCLUSIONS: The T744C polymorphism of the P2Y(12) receptor gene does not modulate platelet response to clopidogrel either in the early or long-term phases of treatment. This specific gene polymorphism alone is therefore unlikely to be the cause of variability in individual response to antiplatelet therapy. 相似文献
10.
Hyperresponsiveness of platelets in ischemic stroke 总被引:2,自引:0,他引:2
Fateh-Moghadam S Htun P Tomandl B Sander D Stellos K Geisler T Langer H Walton K Handschu R Garlichs C Daniel WG Gawaz M 《Thrombosis and haemostasis》2007,97(6):974-978
Platelet activation and aggregation are critical in the pathogenesis of acute ischemic cerebrovascular diseases. The aim of our study was to characterize platelet function in patients with acute ischemic stroke or transient ischemic attack (TIA), and to evaluate the effect of platelet activation on clinical outcome. One hundred thirty-eight consecutive patients with TIA (n = 74) or stroke (n = 64) were enrolled in this study. Platelet aggregation in response to ADP, epinephrine, arachidonic acid, or collagen, and expression of platelet activation receptors (CD62P, CD63, LIBS-1 and PAC-1) in the acute phase and at three months follow-up were evaluated. Platelets derived from stroke patients were more hyperaggregable in response to agonists in the acute phase compared to TIA patients (p[ADP] = 0.002, p[arachidonic acid] = 0.047, p[epinephrine] = 0.020). Platelet activation was enhanced in the acute phase irrespective of the severity of the disease (stroke or TIA) and returned to baseline levels three months later. Persistent elevated platelet activation at three months follow-up (PAC-1) was associated with increased incidence of recurrent stroke (median, [interquartile range] 3.4, [3.0-5.2] versus 2.9, [2.3-4.0], p = 0.048). In conclusion, platelets are hyperactive in acute stroke compared with TIA. A more intensified dual antiplatelet therapy may be of benefit for stroke patients. 相似文献
11.
INTRODUCTION: The marked interindividual variability in platelet inhibition even after administration of high loading doses of clopidogrel raised the question whether monitoring of antiplatelet effects in patients undergoing percutaneous coronary intervention (PCI) can improve clinical outcome. Established methods for monitoring antiplatelet drug activity such as optical aggregometry and determination of surface protein expression are not suitable for routine bedside testing. MATERIAL AND METHODS: We therefore compared the applicability of whole blood impedance aggregometry (20 micromol/L ADP) and the whole blood bedside ULTEGRA assay with ADP-cartridges (20 micromol/L) with optical aggregometry in platelet-rich plasma and determination of surface protein expression (P-Selectin and activated GPIIb/IIIa) by flow cytometry. We analyzed samples obtained from 27 patients scheduled for elective PCI who received a loading dose of 600 mg of clopidogrel. Blood samples were withdrawn before clopidogrel, before PCI and 24h thereafter. RESULTS: Platelet aggregation assessed by optical aggregometry (20 micromol/L ADP) declined from 65+/-9% (baseline) to 42+/-12% (PCI) and 45+/-13% (24h; p<0.01). Expression of surface proteins displayed a similar time course. Platelet aggregation determined by impedance aggregometry decreased from 4.6+/-4.0 Omega (baseline) to 0.1+/-0.3 Omega (PCI) and 0.5+/-1.1 Omega (24h) with no detectable residual platelet aggregation during PCI in 88% of patients. The ULTEGRA assay showed only slight changes after administration of clopidogrel. Correlation analysis between the various assays revealed significant correlations only between optical aggregometry and flow cytometry. CONCLUSIONS: The results indicate that both of the whole blood assays cannot substitute for optical aggregometry or determination of surface proteins in the assessment of clopidogrel-induced platelet inhibition. 相似文献
12.
Marie Lordkipanidz Chantal Pharand Erick Schampaert Donald A. Palisaitis Jean G. Diodati 《Thrombosis research》2009,124(4):418-422
Introduction
Hyporesponsiveness to antiplatelet agents has been linked to an increased risk of major adverse cardiovascular events. However, light transmission aggregometry (LTA), the gold standard methodology for assessing platelet function, requires expertise and is labour-intensive, which render its use in clinical settings impractical. We assessed whether platelet count drop (PCD), a technique widely available in any haematology laboratory, could replace LTA in testing for inhibition of platelet aggregation induced by antiplatelet agents.Materials and methods
One hundred and sixty-one coronary artery disease patients taking aspirin alone and 91 patients taking a combination of aspirin and clopidogrel were enrolled. Platelet aggregation was measured by LTA and PCD stimulated with 1.6 mM of arachidonic acid (AA) for aspirin and 5 and 20 μM of adenosine diphosphate (ADP) for clopidogrel.Results
Correlation between AA-induced LTA and PCD was inexistent (r = - 0.043, p = 0.587), while correlation between ADP-induced LTA and PCD was low (r = 0.374, p < 0.0001 for ADP 5 μM and r = 0.402, p < 0001 for ADP 20 μM). PCD, whether stimulated with AA or ADP, overestimated platelet aggregation as assessed by LTA, by 13-18%. The wide 95% limits of agreement suggest that the assays can disagree significantly in individual patients.Conclusions
Although the PCD method is widely available in non-specialized laboratories, our results demonstrate that there is poor correlation with the current gold standard, i.e. LTA. Thus, PCD should not be used in replacement of LTA to assess antiplatelet responsiveness. 相似文献13.
Argirios E. Tsantes Ignatios Ikonomidis Ioannis Papadakis Stefanos Bonovas Argiri Gialeraki Christine Kottaridi Elias Kyriakou Styliani Kokori Panagiota Douramani Petros Kopterides Petros Karakitsos John Lekakis Violetta Kapsimali 《Thrombosis research》2013
Background
Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel’s antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome.Methods
We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period.Results
Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p = 0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events.Conclusions
PPI co-administration did not influence clopidogrel’s antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay. 相似文献14.
Introduction
Treatment with clopidogrel, a selective platelet P2Y12 receptor antagonist, reduces risk of recurrent ischemic events in patients with acute coronary syndrome (ACS), by limiting platelet aggregation and activation. Stable whole blood clot formation requires activation of platelets, generation of fibrin and final fibrin crosslinks. In this study we intended to compare plasma and whole blood thrombelastography (TEG) measurements in patients during ACS.Materials and Methods
Whole blood and plasma samples from 32 patients with non-ST segment elevation myocardial infarction (NSTEMI) were collected after administration of clopidogrel. Whole blood and plasma fibrin clot strength (MA) were determined by TEG. Platelet aggregation was determined by light transmittance aggregometry (LTA) using adenosine 5'-diphosphate (ADP), thrombin receptor activation peptide (TRAP), or collagen as agonists. Fibrinogen and C-reactive protein (CRP) concentrations were measured by ELISA.Results
Heightened plasma fibrin clot strength was associated with increased platelet reactivity stimulated by ADP (ρ = 0.536; p = 0.002), TRAP (ρ = 0.481; p = 0.007), and collagen (ρ = 0.538; p = 0.01). In contrast to plasma fibrin MA, whole blood MA did not correlate with platelet aggregation. Platelet count was the primary contributor to the difference in thrombin induced whole blood MA and plasma fibrin MA. Increasing levels of CRP were associated with increased plasma fibrin clot strength and platelet reactivity.Conclusions
Our data suggest that inflammation is associated with increased plasma fibrin clot strength and lower platelet inhibition by clopidogrel during ACS. Platelet count is a main contributor to additional contractile force of whole blood TEG as compared to plasma TEG during treatment with clopidogrel. 相似文献15.
目的用血栓弹力图评价缺血性卒中患者正规使用阿司匹林及氯吡格雷后血小板抑制率的变化。方法血栓弹力图检测我院123例住院患者抗血小板药物治疗后花生四烯酸(AA)通路和ADP受体途径诱导的血小板抑制率,患者抗血小板药物治疗包括阿司匹林组(n=7)、氯吡格雷组(n=8)、阿司匹林+氯吡格联合组(n=108)。结果 123例患者中,阿司匹林组AA诱导的血小板抑率为(87.04±22.71)%,氯吡格雷组ADP诱导的血小板抑制率平均值为(46.61±24.43)%,阿司匹林+氯吡格雷组AA和ADP诱导的血小板抑制率为分别(77.87±27.98)%和(50.23±29.27)%。服用阿司匹林和氯吡格雷的患者分别有115和116例,其AA和ADP途径血小板抑制率分别为(78.42±27.69)%;(49.99±28.88)%,差异具有显著统计学意义(P=0.000)。其中对阿司匹林和氯吡格雷敏感者(血小板抑制率≥50%)分别为97例(84.34%)和89例(75.72%),而不敏感者(血小板抑制率<50%)分别为18例(15.65%)和27例(23.28%),两种药物疗效间差异无显著统计学意义(χ2=3.706,P=0.054)。结论服用100mg/d阿司匹林,在绝大多数缺血性脑血管病患者中能产生较强的血小板抑制效应,而服用75mg/d氯吡格雷对血小板抑制稍弱,但多数患者仍能达有效的血小板抑制作用。 相似文献
16.
Background
Recently several alternative forms of the original clopidogrel hydrogensulfate (CHS) were spread worldwide. A large amount of such drugs turned out to be clopidogrel besylate (CB). Only three studies, involving healthy volunteers, investigated the antiplatelet effect of CB, whereas its attribute remained unexplored in the case of patients with cardiovascular diseases. This retrospective study aimed to evaluate the difference between the antiplatelet effects of two clopidogrel formulas, CHS and CB, on patients with coronary artery diseases.Methods
Data of 150 patients with previous CHS treatment were investigated. According to the documentations, the CHS therapy was shifted to CB. 94 patients of the selected population received dual antiplatelet therapy, clopidogrel and aspirin. The antiplatelet effects of CHS and CB were compared by ADP induced platelet aggregation measurements using light transmission aggregometry.Results
Irrespective of the therapeutic combinations the performed statistical investigations failed to show significant difference (p = 0.30) between the effect of CB (AGGmaxCB: 27.6 ± 13.7%) or CHS (AGGmaxCHS: 29.0 ± 15.3%) on the ADP induced platelet aggregation. Insignificant deviations were found in both forms of clopidogrel salts, either in the lack (AGGmaxCB : 32.5 ± 14,2%; AGGmaxCHS: 34,0 ± 16,1%; p = 0,29) or in the presence of aspirin (AGGmaxCB: 24.7 ± 12,5%; AGGmaxCHS: 26,0 ± 14,1%; p = 0,31).Conclusion
Our results indicated that both CB and CHS had an identical inhibitory effect on ADP induced platelet aggregation in patients with cardiovascular diseases. Moreover their efficiency showed no overall significant difference in the case of dual antiplatelet therapy with aspirin as well. However there might be an inter- and intraindividual variability between the two clopidogrel formulas. 相似文献17.
Wallaschofski H Lohmann T Hild E Kobsar A Siegemund A Spilcke-Liss E Hentschel B Stumpf C Daniel WG Garlichs CD Eigenthaler M 《Thrombosis and haemostasis》2006,96(1):38-44
Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically. We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detected a significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors, 21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect, whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone. 相似文献
18.
The difference between clopidogrel responsiveness and posttreatment platelet reactivity 总被引:13,自引:0,他引:13
BACKGROUND: Aggregation is the most common measure of platelet reactivity. The relative inhibition of platelet aggregation between pretreatment and posttreatment is the most common estimate of clopidogrel responsiveness. However, patients responsive to clopidogrel may remain with highly reactive platelets and thus have increased thrombotic risk. METHODS: Platelet reactivity was determined by ADP-induced aggregation (%) in 62 patients undergoing elective coronary stenting at pretreatment and 5 days postprocedure. All patients were on aspirin (325 mg) and received 300 mg of clopidogrel immediately poststenting and 75 mg qd. Pretreatment reactivity was divided into tertiles. Based on clopidogrel drug responsiveness, nonresponders were defined as <10% relative inhibition of pretreatment aggregation, semiresponders as 10-30%, and responders as >30%. We determined the relation between clopidogrel responsiveness and platelet reactivity. RESULTS: Pretreatment reactivity tertiles by 5 microM ADP were: low (47+/-9%), moderate (64+/-4%), and high (78+/-6%). Eight patients were nonresponders, 18 were semiresponders, and 36 were responders. Clopidogrel responsiveness directly correlated with pretreatment reactivity, 86% of responders had moderate or high pretreatment reactivity, whereas 75% of nonresponders had low pretreatment reactivity. Despite being more responsive, 16% of patients with high pretreatment reactivity and 17% with moderate pretreatment reactivity remained with moderate posttreatment reactivity. CONCLUSION: Measuring clopidogrel responsiveness may overestimate the risk of stent thrombosis in nonresponders with low pretreatment reactivity and underestimate risk in those responders who remain with high posttreatment platelet reactivity. Posttreatment platelet reactivity is a better measure of thrombotic risk than responsiveness to clopidogrel. 相似文献
19.
Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement 总被引:45,自引:0,他引:45
Müller I Besta F Schulz C Massberg S Schönig A Gawaz M 《Thrombosis and haemostasis》2003,89(5):783-787
Dual antiplatelet therapy with aspirin and clopidogrel decreases the rate of stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, despite intensified antiplatelet treatment, up to 4.7% of the patients undergoing coronary stenting develop thrombotic stent occlusion, suggesting incomplete platelet inhibition due to clopidogrel resistance. We evaluated the percentage of clopidogrel non-responders among 105 patients with coronary artery disease (CAD) undergoing elective PCI. All patients were treated regularly with aspirin 100 mg/d and received a loading dose of 600 mg clopidogrel followed by a maintenance dose of 75 mg/d before PCI. Clopidogrel non-responders were defined by an inhibition of ADP (5 and 20 Mol/L) induced platelet aggregation that was less than 10% when compared to baseline values 4 h after clopidogrel intake. Semi-responders were identified by an inhibition of 10 to 29%. Patients with an inhibition over 30% were regarded as responders. We found that 5 (ADP 5 Mol/L) to 11% (ADP 20 Mol/L) of the patients were non-responders and 9 to 26% were semi-responders. Among the group of non-responders there were two incidents of subacute stent thrombosis after PCI. We conclude that a subgroup of patients undergoing PCI does not adequately respond to clopidogrel, which may correspond to the occurrence of thromboischemic complications. Point-of-care testing may help to identify these patients who may then benefit from an alternative antiplatelet therapy. 相似文献
20.
Béres BJ Tóth-Zsámboki E Vargová K László A Masszi T Kerecsen G Préda I Kiss RG 《Thrombosis and haemostasis》2008,100(5):829-838
Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure. Alpha-2 adrenoceptor enhances platelet reactivity and might contribute to this phenomenon. For the present study, 121 stable angina patients on standard dual antiplatelet therapy (75 mg clopidogrel and 100 mg acetylsalicylic acid) were recruited. Born aggregometry was performed with adenosine diphosphate (ADP), collagen and epinephrine. To verify platelet adrenergic activity, potentiation by low-dose epinephrine and inhibition by selective alpha-2 receptor blocker atipamezole were determined. To assess the P2Y(12)-specific residual activity, cangrelor was used. Plasma norepinephrine, soluble CD40-ligand, high-sensitivity-C-reactive protein (hsCRP) - and in 24 subjects platelet P-selectin positivity were measured. Epinephrine - at very low concentration (10(-9)g/ml) - significantly potentiates (1.25 microM ADP: 26.5% vs. 43%; 5 microM ADP: 53% vs. 64.5%; collagen: 17% vs 42%, p < 0.001) while atipamezole inhibits ADP- and collagen-induced platelet aggregations (1.25 microM ADP: 26.5% vs. 23%; 5 microM ADP: 53% vs. 47%; collagen: 17% vs. 11%, p < 0.001). Patients with high adrenergic activity have significantly increased baseline ADP- and collagen-induced platelet aggregation. Based on cangrelor's efficacy, these patients have significantly more residual P2Y(12) activity as well. HsCRP and soluble CD40-ligand levels were similar. In conclusion, stable coronary heart disease patients with prominent adrenoceptor activity in vitro have significantly increased platelet aggregability and more functional P2Y(12) receptor, indicating poor inhibitory response to thienopyridines. Therefore, platelet adrenergic receptor represents a considerable, dynamic factor of high residual platelet reactivity and might contribute to cardiovascular events indicating failure of antiplatelet therapy. 相似文献