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Background: The active metabolite of clopidogrel binds the P2Y12 ADP receptor on the platelet surface via a disulfide bond. N-Acetylcysteine (NAC) is able to reduce disulfide bonds. We postulated that NAC might reverse clopidogrel's effect on platelets., Methods: Two groups of patients were investigated. Group 1 included 11 patients with stable coronary disease who, after discontinuation of aspirin, received 14 days of clopidogrel, 75 mg/day. Bleeding time and whole-blood platelet aggregometry (with 5 micromol/L ADP) were compared before and after the 14 days. Patients were then treated with 6 g of NAC orally, followed by repeat measurement of bleeding time and aggregometry. In group 2, 14 patients were treated with clopidogrel (300 mg) and aspirin before a percutaneous coronary intervention. Blood was drawn 22 +/- 3 hours later and divided into 2 samples. One was sent immediately for platelet-rich plasma aggregometry (using 5 and 2 micromol/L ADP, collagen, and arachidonic acid as agonists), thromboelastography, and aggregometry using the Plateletworks assay (Helena Laboratories, Beaumont, Tex). The other sample was treated with NAC (500 mg/L), after which these same platelet function tests were performed., Results: In group 1, NAC therapy did not significantly change the bleeding time or results of aggregometry. In group 2, neither aggregometry nor the Plateletworks assay suggested reversal of inhibition by NAC., Conclusions: These studies reveal that a large dose of NAC does not reduce inhibition of platelet aggregation by clopidogrel in vitro or in vivo.

Introduction: While the CURE trial demonstrated the benefits of clopidogrel in acute coronary syndromes, patients receiving glycoprotein IIb/IIIa antagonists were excluded. Given the frequent coadministration of these two medications, we sought to examine their interaction and their combined effect on platelet inhibition., Methods: Ten patients admitted to the hospital with stable or unstable angina underwent phlebotomy prior to, three hours and six hours after administration of a standard oral loading dose of clopidogrel. The samples were then treated in vitro with incremental concentrations of tirofiban (0, 10, 20, 40, 60, and 80 ng/mL), and optical platelet aggregometry was performed utilizing ADP and TRAP as agonists. We analyzed the combined effects of these agents using a mixed effects model with time and tirofiban concentration as fixed effects, and subject and timing of phlebotomy as random effects., Results: There was no evidence of additional inhibition of platelet aggregation due to clopidogrel regardless of the concentration of tirofiban or the study agonist (ADP 20 muM or iso-TRAP). Specifically, there was no difference in the tirofiban dose-response curves with either platelet agonist for any of the three time points (before, and three and six hours after, clopidogrel administration)., Discussion: There is no evidence that the combination of clopidogrel and tirofiban achieves greater inhibition of platelet aggregation than tirofiban alone.

Background: Dual antiplatelet therapy with aspirin and clopidogrel has replaced aspirin and systemic anticoagulation with warfarin as the preferred antithrombotic therapy after percutaneous coronary intervention (PCI) with stent placement. However, a number of patients have indications for all 3 drugs. We sought to determine the frequency and type of hemorrhagic complications in patients who undergo systemic anticoagulation with warfarin while receiving aspirin and clopidogrel after a PCI with stent placement., Methods: We performed a retrospective analysis of the Mayo Clinic PCI database and identified 66 consecutive patients who were discharged from hospital after PCI between January 2000 and August 2002 (inclusive) receiving a combination of dual antiplatelet therapy (aspirin and clopidogrel) and systemic anticoagulation (warfarin) to determine the incidence of bleeding and other clinical events during the treatment period., Results: Six patients (9.2%; 95% CI, 3.5-19.0) reported a bleeding event; 2 patients required a blood transfusion. No patient died or sustained a myocardial infarction or stent thrombosis., Conclusions: The risk of bleeding may be increased in patients treated with aspirin, a thienopyridine, and warfarin early after PCI with stent placement.

Objectives: The study examined the frequency, correlates, and outcome of patients with stent thrombosis within 30 days of stent placement., Background: Patients in trials evaluating stents or dual antiplatelet therapy to prevent coronary stent thrombosis have generally had narrow inclusion criteria; the extent to which stent thrombosis rates in such trials represent current practice, particularly with the availability of newer stents, is unclear., Methods: We performed a retrospective analysis of the Mayo Clinic Percutaneous Coronary Intervention database and identified all patients who received at least one coronary stent and dual antiplatelet therapy (aspirin and ticlopidine or clopidogrel for two to four weeks)., Results: Four thousand five hundred nine patients underwent successful coronary stent implantation and were treated with dual antiplatelet therapy between July 1, 1994, and April 30, 2000. Stent thrombosis occurred in 23 patients (0.51%; 95% confidence interval 0.32%, 0.76%) within 30 days of stent placement. Multivariate analysis using bootstrap model selection to avoid over-fitting the model indicated that only the number of stents placed was an independent correlate of stent thrombosis (odds ratio 1.80, p < 0.001). The frequency of death and frequency of nonfatal myocardial infarction (MI) among the 23 patients with stent thrombosis were 48% and 39%, respectively., Conclusions: Stent thrombosis is even more rare in the current era than in earlier trials. Number of stents placed was an independent correlate of stent thrombosis. Most patients who suffer stent thrombosis either die or suffer MI.

The IIb/IIIa receptor inhibitors have been shown to improve outcomes following percutaneous coronary intervention (PCI), particularly by decreasing periprocedural myocardial necrosis. Abciximab has been subject to multiple studies, demonstrating consistent improved early and late outcomes in multiple patient populations, including a mortality advantage in diabetics, but there has been concern about the possibility of anaphylaxis, thrombocytopenia, and reduced clinical efficacy with repeat administration of abciximab. Results of the ReoPro Readministration Registry, a prospective, phase IV, multicenter registry of 500 patients undergoing PCI who were treated with abciximab at least 7 days after a previous treatment with this same drug, support the contention that abciximab readministration is both safe and clinically efficacious and that there is no significant increase in the incidence of thrombocytopenia as compared with historical controls of trials of first abciximab administration. However, profound thrombocytopenia did occur with increased frequency as compared with historical controls, suggesting a shift from mild to profound thrombocytopenia with abciximab readministration.