RESUMO
OBJECTIVES: The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non-ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention. BACKGROUND: Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear. METHOD: Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load. RESULTS: After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p < 0.0001), were seen with clopidogrel, but further 80%, 78%, and 72% (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70%, 64%, and 81% (all p < 0.0001) and again further reduced with eptifibatide by 90%, 95%, and 69% (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion. CONCLUSIONS: The activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect.
Assuntos
Aspirina/uso terapêutico , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Idoso , Clopidogrel , Sinergismo Farmacológico , Quimioterapia Combinada , Enoxaparina/uso terapêutico , Eptifibatida , Feminino , Fibrinogênio/efeitos dos fármacos , Fibrinogênio/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Resultado do TratamentoRESUMO
The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH.
Assuntos
Angina Instável/tratamento farmacológico , Anticoagulantes/farmacologia , Biomarcadores/sangue , Dalteparina/farmacologia , Enoxaparina/farmacologia , Heparina/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Fator de von Willebrand/análise , Angina Instável/sangue , Anticoagulantes/uso terapêutico , Plaquetas/química , Feminino , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Estudos ProspectivosRESUMO
Regular and moderate wine consumption is one of the explanations suggested for the lower incidence of cardiovascular events in France compared with other industrialized countries. We evaluated whether alcohol alone or combined with red wine polyphenols reduced plaque size and/or attenuated thrombotic reactivity at the site of advanced atherosclerotic lesions. Red wine extract, or purified (+)-catechin with alcohol, or alcohol alone, was added for 12 weeks to the drinking water of apoE-deficient (apoE(-/-)) C57BL/6 mice and wild-type counterparts. In the apoE(-/-) mice, all alcohol-containing mixtures were associated with a larger size of aortic atherosclerotic lesions. On the other hand, red wine extract and (+)-catechin significantly inhibited blood thrombotic reactivity (P<0.05) as assessed in a cylindrical perfusion chamber model of experimental thrombosis: area reductions in cross-sectional surface of the ex vivo thrombus were 64% and 63%, respectively. In the wild-type mice, red wine extract and (+)-catechin tended to reduce thrombogenicity, which was on the whole less marked than in the apoE(-/-) mice. These findings suggest that a moderate and regular consumption of red wine may protect against clinical cardiovascular events, mainly by attenuating the thrombogenic response rather than by reducing the development of atherosclerotic lesions. This antithrombogenic effect may include normalization of the abnormally high thrombogenic responsiveness in apoE(-/-) mice as well as a direct antithrombotic effect.