Novel Dosing Regimen of Eptifibatide in Planned Coronary Stent Implantation (ESPRIT): A Randomized, Placebo-Controlled Trial - ESPRIT 30 Day Results

Description:

Novel Dosing Regimen of Eptifibatide in Planned Coronary Stent Implantation (ESPRIT): A Randomized, Placebo-Controlled Trial.

Hypothesis:

To determine whether a novel, double-bolus dosing of the gpIIb/IIIa receptor blocker eptifibatide can improve outcomes of patients undergoing coronary stenting.

Study Design

Study Design:

Patients Enrolled: 2064

Primary Endpoints:

A combined major adverse cardiac event endpoint (MACE) including death, MI and target lesion revascularization (TLR) at 12 months follow-up.

Drug/Procedures Used:

Patient with coronary artery disease scheduled to undergo stent implantation were randomized to placebo or to eptifibatide. Eptifibatide administration included two 180 mcg/kg boluses10 minutes apart followed by an infusion of 2 mcg/kg/min for 18–24 hours. A bailout blinded IIb/IIIa receptor was allowed by providing a bailout kit containing eptifibatide for patients randomized to placebo and placebo for patients randomized to eptifibatide. The primary end point was a composite of death, myocardial infarction, urgent target vessel revascularization and thrombotic bailout gpIIb/IIIa inhibitor therapy within 48 hours of randomization. The secondary end point was a composite of death, MI and urgent target vessel revascularization at 30 days.

Principal Findings:

The study was stopped prematurely for efficacy following recommendation of the safety committee after randomization of 1024 patients to placebo and 1040 patients to eptifibatide. The mortality rate was 0.2% in the placebo group and 0.1% in the eptifibatide group (p = 0.55), while the primary end point occurred in 10.5% of placebo treated patients and 6.4% of eptifibatide treated patients (risk ratio 0.63, 95% CI 0.47–0.84, p = 0.0015). This risk reduction was consistent across different components and combination of components of the primary end point (RR 0.65, CI 0.47–0.87 for death/MI/TVR; RR 0.60, CI 0.44–0.82 for death/MI; RR 0.67, CI 0.44–1.03 for large MI; RR 0.60, CI 0.44–0.83 for all MI; RR 0.5, C.I. 0.05–5,42 for death). At 30 days, there was a persistent reduction of the secondary end point from 10.5% to 6.8% (RR 0.65, 95% CI 0.49–0.87, p = 0.0034). Major bleeding was more frequent in the eptifibatide group when compared with placebo (1.3% vs. 0.4%, p = 0.027). No significant differences in the incidence of major bleeding were observed in the lowest tercile of activated clotting time (ACT<244 s, 0.6% major bleed in the eptifibatide group and 0.6% in the placebo group).

A double bolus of eptifibatide is safe and effective in reducing acute and 30 days adverse outcomes in patients undergoing stent implantation.

Interpretation:

This study confirms the acute results of the EPISTENT trial, and it suggests that routine use of gpIIb/IIIa receptor blockers should become standard of care for patients undergoing stent implantation.

References:

1. The ESPRIT Investigators. Lancet 2000;356:2037-4.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease

Keywords: Odds Ratio, Coronary Artery Disease, Myocardial Infarction, Platelet Aggregation Inhibitors, Peptides, Risk Reduction Behavior, Standard of Care, Stents, Platelet Glycoprotein GPIIb-IIIa Complex


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