We sought to compare the efficacy of tirofiban and abciximab on platelet inhibition as well as their effects of platelet inhibition on C-reactive protein levels during percutaneous coronary intervention (PCI).
Using a randomized, double-blind study design, 95 consecutively eligible patients were randomized to receive either tirofiban or abciximab before undergoing native coronary artery revascularization with a stent. Clinical endpoints were death, nonfatal MI, target vessel revascularization (TVR) with coronary artery bypass grafting or PCI within 30 days of the study procedure. The medications were compared for differences in platelet aggregation as measured by a rapid function platelet assay, as well as measurements of the inflammatory marker C-reactive protein (CRP) at frequent intervals following drug administration during PCI.
A total of 95 patients were randomized to abciximab (n = 44) or tirofiban (n= 51). There was no significant difference in platelet aggregation documented throughout the procedure (10-, 20-, 30-, 45-minute time points). In diabetic patients abciximab had significantly lower platelet inhibition as compared to tirofiban at 10 minutes (84.17 +/- 8.28% vs. 90.40 +/- 5.79%; p = 0.0097). Using a Spearman correlation coefficient model, hs-CRP demonstrated an inverse relationship with platelet inhibition over time (-0.7307, p = 0.0002) in patients treated with abciximab.
There is no major difference in platelet inhibition between tirofiban and abciximab during PCI. In this study, tirofiban showed a greater inhibition in diabetic subsets at the first time point within PCI. Platelet inhibition may be inversely related to the levels of CRP during PCI.
[Show abstract][Hide abstract] ABSTRACT: Apart from the central beneficial role platelets play in hemostasis, they are also involved in atherothrombotic diseases. Here, we review the current knowledge of platelet intracellular signal transduction pathways involved in platelet adhesion, activation, amplification of the activation signal and aggregation, as well as pathways limiting platelet aggregation. A thorough understanding of these pathways allows explanation of the mechanism of action of existing antiplatelet agents, but also helps to identify targets for novel drug development.
Clinical Chemistry and Laboratory Medicine 11/2010; 48 Suppl 1(1):S3-13. DOI:10.1515/CCLM.2010.363 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is cumulative evidence that the degree of inflammation correlates with prognosis after percutaneous coronary interventions (PCI). Additionally, there is a cross-link between platelet activation and inflammatory pathways. The aim of the present analysis was to evaluate the association of inflammatory markers and effects of dual antiplatelet therapy on platelet function and outcome in patients undergoing PCI.
In a pilot study, 157 patients with symptomatic coronary artery disease (CAD) undergoing PCI were consecutively evaluated. Platelet response to clopidogrel and acetylsalicylic acid was assessed using whole blood multiple electrode aggregometry (MEA). Baseline levels of IL-6, RANTES and MCP-1 were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Levels of IL-6, RANTES, and CRP correlated well with ADP and arachidonic acid (AA)-induced MEA. In a second step, a retrospective analysis of a cohort of 903 PCI-patients was performed to evaluate the association of on-treatment residual platelet aggregation (RPA) and baseline CRP levels on the incidence of myocardial infarction (MI), death and stent thrombosis (ST). Patients suffering a subsequent event had a significantly higher level of baseline CRP and higher RPA compared to patients without events. After multivariate adjustment high baseline CRP and high RPA were independent predictors for combined major events and ST after PCI.
To our knowledge this is the first study linking inflammation, antiplatelet drug responsiveness and outcome in a large CAD-patient cohort. The results suggest a relevant interaction of these parameters and encourage multimodal therapeutic approaches to treat cardiovascular risk after PCI.
[Show abstract][Hide abstract] ABSTRACT: Platelet releasate has been shown to promote osteogenetic cell proliferation and differentiation. Topography and chemistry of biomaterials have high impact on platelet activation. More specifically, the bioactive cell adhesive peptide sequence Arg-Gly-Asp (RGD) triggers platelet activation mediated by the α(IIb) β(3) integrin receptor. Accordingly, topographical, chemical and biomimetical (immobilized RGD peptide) modifications of titanium (Ti) surfaces may enhance early platelet activation and bony healing of implants. Therefore, the aim of the study was to evaluate platelet activation with subsequent platelet-derived cytokine release by accordingly modified Ti surfaces.
Pre-treated (PT; mean roughness [R(a)]=0.04 μm, contact angle [CA]=91°), acid-etched (A, R(a) =0.83 μm, CA=106°), large grit-sandblasted, acid-etched (SLA, R(a) =3.2 μm, CA=109°) as well as hydrophilically modified acid-etched (modA, R(a) =0.83 μm, CA=0) and modified large grit-sandblasted, acid-etched (modSLA, R(a) =3.2 μm; CA=0°) titanium surfaces were investigated. Additionally, RGD peptides were chemically immobilized on PT, A and SLA surfaces (PT-RGD [CA=18°], A-RGD [CA=0°], SLA-RGD [CA=0°]). The different Ti surfaces were incubated with platelet concentrate of three healthy volunteers at room temperature for 15 min and for 30 min. High thrombogenous collagen served as the control group. Out of the supernatant, platelet consumption was assessed via platelet count (PC). Cytokine release was quantified via the level of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF).
After 15 min, especially the rough SLA surface showed a strong decrease in PC and a strong increase in VEGF and PDGF levels. After 30 min, high platelet consumption as well as high levels of VEGF and PDGF were measured for unspecifically modified (modA) and especially for biomimetic, specifically modified (PT-RGD, A-RGD) surfaces, indicating a delayed effect of the surface modifications on platelet activation.
Modifications of surface roughness modifications appear to influence early platelet activation and cytokine release after 15 min whereas surface chemistry modifications with increased hydrophilic properties and surface modifications via RGD peptide on plainer surfaces lead to a further, more specific promotion of platelet activation and degranulation after 30 min. The observed effect could be valuable for critical clinical situations like compromised bone sites.
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