Dual antiplatelet therapy

Superiority of Dual Antiplatelet Therapy (Thienopyridine Plus Aspirin) Over Coumadin Plus Aspirin in PCI Patients
Several studies during the early stent era demonstrated the superiority of the combination of ticlopidine plus aspirin over coumadin plus aspirin. has deployment. While progress was made over coumadin, Ticlopidine itself was associated with side effects and complications which included neutropenia in > 1%, thrombotic thrombocytopenia purpura in 0.2%, rash, nauseaand diarrhea. Given the improved side effect profile and the results of the CLASSICS study, clopidogrel has replaced ticlopidine as the thienopyridine of choice.

Data is Lacking Regarding the Safety and Efficacy of Thienopyridine Monotherapy Versus Thienopyridine Plus Aspirin Therapy in the Aspirin Intolerant Patient
One question that arises among patients who have aspirin hypersensitivity is the safety and efficacy of thienopyridine monotherapy in the mangement of the PCI patient including those who have been stented. There is one single center, small randomized trial purporting to compare the safety and efficacy of thienopyridine monotherapy to that of thienopyridine plus aspirin. 378 stents were placed in 243 patients who were randomly assigned to treatment with either 2 x 250 mg of ticlopidine (n=121) or the combination of 2 x 250 mg ticlopidine + 100 mg aspirin (122 patients) daily. All patients received 500 mg of intravenous aspirin at the time of the procedure. Two hundred and thirty-seven patients (97.5%) were free from the primary endpoint of death, cardiac events and vascular access-site complications through three months with no differences between treatment groups. Although 2 stent thromboses were observed in the combined treatment group, none were observed in the ticlopidine monotherapy group. There are several important limitations to this study. One is the fact that all patients received a high (500 mg) intravenous aspirin during the PCI which would have led to significant levels of platelet inhibition over the next week due to irreversible acetylation and inhibition of prostaglandin H-synthase/cyclooxygenase. This is a period of high vulnerability to stent thrombosis and ischemic complications. Thus, this was not truly a study of thienopyridine monotherapy as all patients received intravenous aspirin. The study by Machraoui is also limited by its small sample size. Finally, the study administered ticlopidine, which is not a pro-drug and may be associated with a lower rate of hyporesponsiveness than clopidogrel.

Data Inidicating that the Addition of Aspirin to a Thienopyridine Improves Clinical Outcomes in Patients with Acute Coronary Syndromes
There is surrogate marker data indicating that the level of platelet inhibition is greater among patients in whom aspirin is added to a thienopyridine. In one study, aspirin added to clopidogrel was associated with a greater degree of inhibition of collagen-induced aggregation. The level of platelet aggregation for the combination was only 16.4 +/- 2.4%, which is less than that for aspirin alone (36.5 +/- 4.2%) or clopidogrel alone (59.3 +/- 5.1%, 3 way p < 0.001). Further, aspirin added to clopidogrel was more effective than either aspirin or clopidogrel alone after activation with low dose thrombin (p < 0.05). In rabbit models of stent thrombosis, aspirin potentiated the antithrombotic activity of clopidogrel in the following models: 1)thrombosis induced by a silk thread; 2) thrombosis in stents placed in an arteriovenous shunt; 3) thrombus formation following electrical stimulation of the rabbit carotid artery; and 4) 111In-labeled platelet deposition on a stent implanted in an arteriovenous shunt. The clinical benefit of adding aspirin to clopidogrel is also demonstrated indirectly by the following observation: among patients on clopidogrel, patients with stent thrombosis were more often resistant to aspirin.