Clopidogrel Reduces ADP-Induced Expression of Platelet-derived CD40L 0.5 Control 0.4 ADP 30 M 0.3 P<0.05 vs ADP-stimulated controls CD40L Expression (Mn X) 0.2 CD40 ligand (CD40L) is a cell-surface molecule that is expressed on activated T cells and platelets. CD40L gets translocated to the platelet surface following stimulation. In this study, 10 healthy male volunteers were treated with either clopidogrel (75 mg/d for 7 days) or ASA (100 M in vitro), and the ADP-induced expression of CD40L was determined. Results demonstrated that clopidogrel completely abolished the expression of CD40L. This may indicate that stimulation of the P2YAC ADP receptor is required for CD40L translocation to the platelet membrane. 0.1 Control ASA* Clopidogrel† ASA* + clopidogrel† * ASA 100 M in vitro. † Clopidogrel 75 mg/d for 7 days. Hermann A, et al. Platelets. 2001;12:74-82. Hermann A, Rauch BH, Braun M, et al. Platelet CD40 ligand (CD40L)—subcellular localization, regulation of expression, and inhibition by clopidogrel. Platelets. 2001;12:74-82.

Clopidogrel Therapy May Reduce the Risk Associated With Elevated Baseline CRP Status Death or MI by Day 30 in Patients Undergoing PCI With Stenting No thienopyridine pretreatment 24% n=74 25 Thienopyridine pretreatment 20 13% n=295 Percent 15 10.2% n=136 10% n=565 Evidence links an elevated baseline inflammatory status to adverse events in patients undergoing PCI. C-reactive Protein (CRP) is associated with higher death and acute myocardial infarction (AMI) within 30 days of follow-up and is also associated with an increase in target vessel revascularization. In this study, patients undergoing coronary stenting who were pretreated/not pretreated with clopidogrel were drawn from a consecutively compiled PCI registry at the Cleveland Clinic. The study population was limited to those receiving stents to avoid the confounding influence of the lack of continued clopidogrel therapy in patients not receiving stents. Baseline CRP levels were measured prior to coronary intervention. The rate of 30-day death or AMI increased progressively with increasing baseline CRP in both patient groups. Although there was no overall difference in 30-day death or AMI across all CRP quartiles in pretreatment vs no pretreatment, there was a significant difference in patients with the highest baseline CRP (>1.1 mg/dL; 58% RRR). 10 58% RRR P= 0.002 5 Total Population 0-<1.1 mg/dL Highest Quartile >1.1 mg/dL Chew DP, et al. Am J Cardiol. 2001;88:672-674. Chew DP, Bhatt DL, Robbins MA, et al. Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein. Am J Cardiol. 2001;88:672-674.

Increasing Baseline CRP and 30-Day Death/MI Thienopyridine pretreatment No thienopyridine pretreatment * 35 30 25 20 30-Day Death/MI (%) † 15 Evidence on the role of inflammation in causing major adverse cardiovascular events has been accumulating in the literature. The levels of CRP in the serum have been shown to be predictive of post-procedural complications and events.1,2 Chew et al have analyzed the effect of thienopyridine pretreatment on risk of death or MI within 30 days in patients undergoing PCI for stenting. Patients were divided into quartiles based on their CRP levels (<0.3 mg/dL, 0.3-0.5 mg/dL, 0.5-1.1 mg/dL, and >1.1 mg/dL). The rate of death or AMI within 30 days increased progressively with increasing CRP quartiles—6%, 10%, 12%, and 15%, respectively. Clopidogrel pretreatment was not associated with a significant reduction in 30-day death or AMI with the overall population, but pretreatment was associated with a 58% RRR in those patients in the highest quartile.3 10 5 <0.3 mg/dL 0.3-0.5 mg/dL 0.5-1.1 mg/dL >1.1 mg/dL *2 for trend P = 0.002 †2 for trend P = 0.125 Chew DP, et al. Am J Cardiol. 2001;88:672-674. CRP Quartiles Chew DP, Bhatt DL, Robbins MA, et al. Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention. Circulation. 2001;104:992-997. Gaspardone A, Crea F, Versaci F, et al. Predictive value of C-reactive protein after successful coronary-artery stenting in patients with stable angina. Am J Cardiol. 1998;82:515-518. Chew DP, Bhatt DL, Robbins MA, et al. Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein. Am J Cardiol. 2001;88:672-674.