Effects of pretreatment with clopidogrel on platelet and coagulation activation in patients undergoing elective coronary stenting

Background: Current data suggest that pretreatment with clopidogrel (in addition to aspirin) prior to elective percutaneous coronary intervention (PCI) might be associated with a reduced incidence of subsequent adverse ischemic events. The aim of this placebo-controlled study was to find out whether an extended pretreatment period with clopidogrel before an elective PCI might confer a superior inhibition of the platelet activation and aggregation than clopidogrel given not until PCI. Methods: Twenty patients with stable angina being already on aspirin were randomly assigned to receive the loading dose of 300 mg clopidogrel, either 24 h before or immediately after stent implantation. At several time points before and after PCI, the activation of both the platelet and the coagulation system was determined by measuring thromboglobulin (beta-TG) and prothrombin fragment f1.2 (f1.2), respectively, in venous blood and in blood emerging from a microvascular injury (shed blood). Results: Pretreatment with clopidogrel before PCI exhibited a slight reduction of beta-TG (from 178 to 139 ng/ml, p = 0.085) and of f1.2 (from 0.81 to 0.75 nmol/l, p = 0.045) in venous blood. Heparin administration (at the beginning of PCI) resulted in a 65% inhibition of beta-TG (from 10,590 to 2833 ng/ml) and 90% inhibition of f1.2 formation (from 38.7 to 4.2 nmol/l) in shed blood of patients with clopidogrel pretreatment. The extent of inhibition was, however, comparable to that observed in patients without clopidogrel pretreatment (beta-TG: from 8025 to 2812 ng/ml, 76% inhibition, p = 0.47; f1.2: from 34.9 to 3.8 nmol/l, 86% inhibition, p = 0.80). After PTT normalisation (6 h after PCI), levels of beta-TG and f1.2 both in venous blood and in shed blood did not differ between the two treatment regimens up to 48 h after PCI. Conclusion: Pretreatment with clopidogrel did not result in a pronounced inhibition of the platelet and coagulation system activation in patients on aspirin undergoing elective coronary stent implantation. (C) 2003 Elsevier Ltd. All rights reserved.