Ticlopidine Pretreatment Before Coronary Stenting Is associated With Sustsained Decrease of Adverse Cardiac Events: Data From the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (Epistent Trial) - EPISTENT Trial Ticlopidine Pre-treatment Substudy

Description:

Ticlopidine Pretreatment Before Coronary Stenting Is associated With Sustsained Decrease of Adverse Cardiac Events: Data From the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (Epistent Trial).

Hypothesis:

To determine whether pretreatment with ticlopidine before coronary stenting results in a sustained decrease in adverse cardiac events.

Study Design

Study Design:

Patients Enrolled: 1603

Primary Endpoints:

The primary end points were a composite of all-cause mortality, nonfatal MI or urgent revascularization at 30 days and a composite end point of all-cause mortality, nonfatal MI and target vessel revascularization (TVR) at 1 year, as well as its individual components.

Drug/Procedures Used:

The study sample included 1603 patients enrolled in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT trial) who where randomized to receive either placebo or abciximab. Of these, 932 patients received pretreatment with ticlopidine before stenting at the discretion of the investigator. All patients were pretreated with aspirin, and all patients were treated with ticlopidine after stent implantation.

Principal Findings:

At 30 days follow-up, the primary end point had occurred in 13.4% of patients in the placebo (no abciximab or ticlopidine) group, 8.9% of patients in the placebo + ticlopidine group, 5.5% of patients in the abciximab/no ticlopidine group (p=0.028 vs. placebo & plus; ticlopidine) and 5.2% of patients in the abciximab + ticlopidine group. In the placebo group, the benefit of pretreatment was primarily due to a decrease in the occurrence of myocardial infarction (8.4% vs. 12.5%, p=0.048). At 1-year follow-up, the incidence of the primary end point was significantly lower in the placebo group in patients pretreated with ticlopidine when compared to patients not pretreated with ticlopidine (20.7% vs. 28.5%, p=0.008), while there was no difference related to pretreatment with ticlopidine in the abciximab group (19.5% for abciximab + ticlopidine vs. 20.9% for abciximab/no ticlopidine). After adjustment for baseline characteristics and propensity of being on ticlopidine, pretreatment with ticlopidine was an independent predictor of lower need for TVR at 1 year (hazard ratio, 0.62: 95% CI, 0.43-0.89; p=0.010). By multivariate modeling, the beneficial effect of ticlopidine on TVR was however diminished by treatment with abciximab.

Pretreatment with ticlopidine before stent implantation results in a sustained decrease of a combined end point including death, myocardial infarction and TVR in patients not receiving abciximab and of TVR in all patients.

Interpretation:

An important limitation is that the duration of pretreatment with ticlopidine was unknown. Thus, it is unknown if steady-state concentrations of ticlopidine had been reached at the time of stent implantation. However, the study highlights the importance of platelet inhibition during stent implantation, and it raises several issues. Aspirin resistance is a known entity, and it is possible that the beneficial effect of ticlopidine in the placebo-treated group was due not only to its additional antiplatelet effect but also to an antiplatelet effect in aspirin-resistant patients. Second, it is interesting to note how the initial superiority of abciximab over placebo plus ticlopidine appeared to be lost at 1-year follow up.

References:

1. Steinhubl R, Ellis SG, Wolski K, et al. Circulation 2001;103:1403-9.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Ticlopidine, Blood Platelets, Immunoglobulin Fab Fragments, Stents


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