RESUMEN
Platelets are involved in thrombus formation and inflammation following vascular injury, while clopidogrel exerts antithrombotic and anti-inflammatory actions. We investigated various platelet-derived prothrombotic and proinflammatory mediators as well as the platelet aggregatory response in patients with acute coronary syndromes (ACS) receiving clopidogrel, as a function of the patient responsiveness to drug treatment. Blood samples were obtained from 40 patients with recent (<24 h) ACS before clopidogrel loading 600 mg (followed by a maintenance dose of 75 mg/day) as well as 5-days and 30-days afterwards. Twelve patients exhibited platelet reactivity index (PRI) values higher than 50% evaluated by the Vasodilator Stimulated Phosphoprotein (VASP) test at 5 days and were characterized as nonresponders. The platelet response to adenosine diphosphate (ADP) and thrombin receptor agonist peptide-14 (TRAP) was studied by flow cytometry and light transmission aggregometry. A maximum reduction of ADP- or TRAP-induced platelet aggregation in 28 clopidogrel responding patients was observed at 5 days postclopidogrel loading, whereas in nonresponders, it was achieved at 30-days along with a significant decrease in the PRI values. Similar results were obtained for the membrane expression of CD40L and the production of platelet-derived microparticles. By contrast, the maximum inhibition of P-selectin expression and platelet-leukocyte conjugate formation was observed at 30-days in both patient groups. A maintenance dose of 75 mg clopidogrel differentially affects the platelet aggregation and platelet-derived prothrombotic and proinflammatory mediators in ACS patients within the first month of the treatment, a phenomenon that is highly influenced by the drug response variability. Since these factors may be involved in the major adverse cardiovascular events in ACS patients, especially in those undergoing percutaneous coronary intervention, the above findings may be clinically important.
Asunto(s)
Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/tratamiento farmacológico , Plaquetas/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Ticlopidina/análogos & derivados , Adenosina Difosfato/farmacología , Plaquetas/fisiología , Clopidogrel , Esquema de Medicación , Femenino , Citometría de Flujo , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/farmacología , Proyectos Piloto , Ticlopidina/uso terapéuticoRESUMEN
OBJECTIVE: The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. In this study we compared the antiplatelet effectiveness of a generic clopidogrel salt, clopidogrel besylate (CB), with the original CHS in patients with an ACS. RESEARCH DESIGN AND METHODS: Ninety-six ACS patients were randomized to receive a 600-mg loading dose of either CHS (n = 45) or CB (n = 51), followed by 75 mg/day. Sixty-eight patients underwent a percutaneous coronary intervention (PCI), whereas 28 were treated conservatively. Platelet aggregatory response, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression and platelet-leucocyte conjugates were determined before clopidogrel loading (baseline), as well as at 5 days and at 1 month afterwards. RESULTS: No difference in the clopidogrel response variability was observed between patients receiving CHS or CB either at 5 days or at 1 month of follow-up. Similarly, no difference in the inhibition of platelet aggregation, P-selectin expression or in the platelet-leucocyte conjugates was observed between CHS and CB group during the follow-up. CONCLUSIONS: There is no overall significant difference in the antiplatelet efficacy between CB and CHS during their administration in ACS patients for up to 1 month after the episode.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/sangre , Anciano , Clopidogrel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Ticlopidina/uso terapéuticoRESUMEN
The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. We compared the antiplatelet effectiveness of long-term administration of the original CHS with a generic clopidogrel besylate (CB) salt formulation in 86 patients with a history of an ACS. At 1 month after the episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n = 41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and platelet-leucocyte conjugates were determined before randomization and at 6 months afterward. No difference in any platelet parameter studied was observed between the 2 groups either before randomization or after 6 months of treatment with CHS or CB. We conclude that there is no difference in the antiplatelet efficacy between CB and CHS during long-term administration in patients with a history of an ACS.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Medicamentos Genéricos/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/sangre , Clopidogrel , Medicamentos Genéricos/efectos adversos , Humanos , Cuidados a Largo Plazo , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: Mixed dyslipidemia, oxidative stress and inflammation are related to a high risk for cardiovascular events. The aim of this open-label randomized study was to compare the effects of high-dose rosuvastatin, low-dose rosuvastatin plus fenofibrate and low-dose rosuvastatin plus omega 3 fatty acids on inflammation and oxidative stress indices in patients with mixed dyslipidemia. METHODS: Ninety patients with mixed dyslipidemia participated in the study. Patients were randomly allocated to receive rosuvastatin 40 mg (n = 30, group R), rosuvastatin 10 mg plus fenofibrate 200 mg (n = 30, group RF) or rosuvastatin 10 mg plus omega 3 fatty acids 2 g daily (n = 30, group RΩ). Plasma and high-density lipoprotein (HDL)-associated lipoprotein-associated phospholipase A2 (LpPLA2) activities, high-sensitivity C reactive protein (hsCRP), plasma isoprostane and paraoxonase (PON1) activities were measured at baseline and after 3 months of treatment. RESULTS: Serum concentrations of non-HDL cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly reduced in all study groups. However, these changes were more pronounced in the rosuvastatin monotherapy group. In all treatment groups a significant reduction in total plasma LpPLA2 activity was observed (by 41, 38 and 30% for groups R, RF and RΩ, respectively). This decrease was greater in the R and RF groups compared with the RΩ combination (p < 0.05). HDL-LpPLA2 activity was increased more in the RF group (+43%) compared with the R and RΩ groups (+ 18% and + 35%, respectively; p < 0.05 for both comparisons). In all treatment groups there was a nonsignificant reduction in plasma 8-iso-PGF2α levels. A 53% reduction of hsCRP levels was observed in the R group, while in the RF and RΩ groups the reduction was 28 and 23%, respectively (p < 0.05 and p < 0.01 for the comparisons of group R with groups RF and RΩ, respectively). No significant changes were observed in PON activities in all treatment groups. CONCLUSION: The greater non-HDL-C- and LDL-C-lowering efficiency of rosuvastatin monotherapy along with its more potent effect on LpPLA2 activity and hsCRP levels indicate that this regimen is a better treatment option for patients with mixed dyslipidemia.