thrombin-receptor-peptide-(42-55) and Coronary-Disease

The antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins. We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes (ACS) could affect the antiplatelet potency of clopidogrel.. Forty-five hypercholesterolemic patients with the first episode of an ACS were included in the study. Patients were randomized to receive daily either 10 mg of atorvastatin (n=21) or 40 mg of pravastatin (n=24). Thirty patients who underwent percutaneous coronary intervention (PCI) received a loading dose of 375 mg of clopidogrel, followed by 75 mg/d for at least 3 months. In the remaining 15 patients who refused to undergo PCI, clopidogrel therapy was not administered. Eight normolipidemic patients with the first episode of an ACS were also included and received only clopidogrel. The serum levels of soluble CD40L and the adenosine 5'-diphosphate- or thrombin receptor activating peptide-14-induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline (within 30 minutes after admission) and 5 weeks later. Neither atorvastatin nor pravastatin significantly influenced the clopidogrel-induced inhibition of platelet activation, nor did clopidogrel influence the therapeutic efficacy of atorvastatin.. Atorvastatin does not affect the antiplatelet potency of clopidogrel when coadministered for 5 weeks in ACS patients.

Topics: Acute Disease; Adenosine Diphosphate; Aged; Angioplasty, Balloon, Coronary; Atorvastatin; CD40 Ligand; Clopidogrel; Combined Modality Therapy; Coronary Disease; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Administration Schedule; Drug Interactions; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inactivation, Metabolic; Male; Middle Aged; P-Selectin; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Pravastatin; Pyrroles; Stents; Ticlopidine; Treatment Outcome

The antiplatelet potency of clopidogrel may be attenuated by short-term co-administration of lipophilic statins metabolized through the cytochrome P-450, isoform 3A4. We investigated whether the co-administration of atorvastatin (20?mg/day) for 5 weeks, in patients with acute coronary syndromes (ACS) could affect the antiplatelet activity of clopidogrel. Fifty-one patients with the first episode of an ACS were included in the study. All patients underwent percutaneous coronary intervention (PCI) and received a loading dose of 375 mg of clopidogrel, followed by 75 mg/day for at least 3 months. Twenty-six of them presented with low density lipoprotein (LDL) cholesterol levels >100?mg/dl (2.6 mmol/l) (measured within 24 h from the onset of symptoms) and received daily 20 mg/day of atorvastatin. The ADP- or TRAP-induced platelet aggregation, as well as P-selectin and CD40L surface expression, were studied at baseline (within 30 min after admission) and 5 weeks afterwards. Atorvastatin did not influence either the clopidogrel-induced inhibition of platelet aggregation initiated by 5 or 10 microM ADP or the clopidogrel-induced reduction of the membrane expression of P-selectin and CD40L induced by ADP. In conclusion, atorvastatin, even at a dose of 20 mg/day does not affect the antiplatelet efficacy of clopidogrel when co-administered for 5 weeks in ACS patients.

Topics: Acute Disease; Adenosine Diphosphate; Aged; Angioplasty, Balloon, Coronary; Anticholesteremic Agents; Atorvastatin; Blood Platelets; CD40 Ligand; Cholesterol; Cholesterol, LDL; Clopidogrel; Coronary Disease; Drug Administration Schedule; Drug Interactions; Female; Flow Cytometry; Heptanoic Acids; Humans; Male; Middle Aged; P-Selectin; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyrroles; Ticlopidine; Triglycerides

We sought to examine whether patients with stable coronary artery disease (CAD) have increased platelet reactivity and an enhanced propensity to form monocyte-platelet aggregates.. Platelet-dependent thrombosis and leukocyte infiltration into the vessel wall are characteristic cellular events seen in atherosclerosis.. Anticoagulated peripheral venous blood from 19 patients with stable CAD and 19 normal control subjects was incubated with or without various platelet agonists and analyzed by whole blood flow cytometry.. Circulating degranulated platelets were increased in patients with CAD compared with control subjects (mean [+/- SEM] percent P-selectin-positive platelets: 2.1 +/- 0.2 vs. 1.5 +/- 0.2, p < 0.01) and were more reactive to stimulation with 1 micromol/liter of adenosine diphosphate (ADP) (28.7 +/- 3.9 vs. 16.1 +/- 2.2, p < 0.01), 1 micromol/liter of ADP/epinephrine (51.4 +/- 4.6 vs. 37.5 +/- 3.8, p < 0.05) or 5 micromol/liter of thrombin receptor agonist peptide (TRAP) (65.7 +/- 6.8 vs. 20.2 +/- 5.1, p < 0.01). Patients with stable CAD also had increased circulating monocyte-platelet aggregates compared with control subjects (percent platelet-positive monocytes: 15.3 +/- 3.0 vs. 6.3 +/- 0.9, p < 0.01). Furthermore, patients with stable CAD formed more monocyte-platelet aggregates than did control subjects when their whole blood was stimulated with 1 micromol/liter of ADP (50.4 +/- 4.5 vs. 28.1 +/- 5.3, p < 0.01), 1 micromol/liter of ADP/epinephrine (60.7 +/- 4.3 vs. 48.0 +/- 4.8, p < 0.05) or 5 micromol/liter of TRAP (67.6 +/- 5.7 vs. 34.3 +/- 7.0, p < 0.01).. Patients with stable CAD have circulating activated platelets, circulating monocyte-platelet aggregates, increased platelet reactivity and an increased propensity to form monocyte-platelet aggregates.

Topics: Adenosine Diphosphate; Adult; Angina Pectoris; Cell Adhesion; Cell Adhesion Molecules; Cell Count; Cell Degranulation; Cell Movement; Coronary Artery Disease; Coronary Disease; Coronary Vessels; Epinephrine; Female; Flow Cytometry; Humans; Leukocytes; Male; Middle Aged; Monocytes; P-Selectin; Peptide Fragments; Platelet Activation; Platelet Aggregation; Receptors, Thrombin; Thrombosis