Eptifibatide Bolus Research Articles

Design and methodology of the ESPRIT trial: Evaluating a novel dosing regimen of eptifibatide in percutaneous coronary intervention

Background Clinical trials of the glycoprotein (GP) IIb/IIIa inhibitors have shown that these potent antiplatelet agents are effective in reducing the ischemic complications of percutaneous coronary interventions. However, even though stents are now implanted in >75% of percutaneous interventional procedures, only one study, a trial of the monoclonal antibody abciximab, has formally evaluated adjunctive GP IIb/IIIa inhibition in this setting. Methods and Results Eptifibatide, a nonimmunogenic and rapidly reversible inhibitor of the platelet receptor integrin IIb/IIIa, has also undergone evaluation as an adjunct to coronary intervention. In clinical trials performed heretofore, however, it has appeared to have less relative clinical efficacy than the monoclonal antibody abciximab. Since the early seminal trials, it has been recognized that the doses of eptifibatide previously used achieved only 30% to 50% of maximal platelet GP IIb/IIIa integrin inhibition. This is considerably less than the 80% level of receptor inhibition that has been proposed to prevent coronary thrombus formation in animal models and that has been achieved in clinical trials with abciximab. Conclusions The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial was designed to test the safety and efficacy of a high-dose, “180/2.0/180” double-bolus regimen of eptifibatide (a 180-μg/kg bolus followed 10 minutes later by a second 180-μg/kg bolus of eptifibatide combined with a 2.0-μg/kg per minute infusion) as an adjunct to nonacute percutaneous coronary intervention with stent implantation. In this report, we review the rationale, design, and methods of this clinical investigation. (Am Heart J 2000;140:834-9.)

Cigarette smoking status and outcome among patients with acute coronary syndromes without persistent ST-segment elevation: Effect of inhibition of platelet glycoprotein IIb/IIIa with eptifibatide

Background Studies have shown that cigarette smokers constitute a substantial proportion of patients with acute coronary syndromes (ACS) and have platelet-rich coronary thrombi. We characterized the influence of smoking status on outcome of patients with ACS without persistent ST-segment elevation and tested the hypothesis that selective inhibition of the platelet glycoprotein IIb/IIIa receptor with eptifibatide would improve outcomes among cigarette smokers. Methods The study of population included patients enrolled in the PURSUIT trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) with known smoking status presenting with ischemic chest pain ≤24 hours and having either ischemic electrocardiographic changes without persistent ST-segment elevation or elevated creatine kinase MB levels. Patients were randomly assigned to receive a bolus and infusion of either eptifibatide or placebo in addition to standard therapy. The primary end point was a composite of death or nonfatal myocardial infarction within 30 days. Results of the 9406 patients with known smoking status, 2677 were current smokers, 3086 were former smokers, and 3643 were nonsmokers. Cigarette smokers had better 30-day outcomes (12.3%, 16.8%, and 15.4% for smokers, former smokers, and nonsmokers, respectively; P = .001). However, after adjusting for differences in baseline clinical variables, smoking status was not a predictor of 30-day outcome ( P = .45). There was a reduction in the composite end point overall with eptifibatide compared with placebo (14.3% vs 15.7%, P = .054) but no interaction between smoking status and treatment strategy ( P = .68). Conclusions Among patients with ACS without persistent ST-segment elevation, cigarette smokers had better short-term outcomes because of their more favorable clinical profile. Although prior studies have suggested that smokers more commonly have platelet-rich thrombi than nonsmokers, eptifibatide did not result in more improvement in their outcome compared with former smokers or nonsmokers.

Cigarette smoking status and outcome among patients with acute coronary syndromes without persistent ST-segment elevation: Effect of inhibition of platelet glycoprotein IIb/IIIa with eptifibatide

Background Studies have shown that cigarette smokers constitute a substantial proportion of patients with acute coronary syndromes (ACS) and have platelet-rich coronary thrombi. We characterized the influence of smoking status on outcome of patients with ACS without persistent ST-segment elevation and tested the hypothesis that selective inhibition of the platelet glycoprotein IIb/IIIa receptor with eptifibatide would improve outcomes among cigarette smokers. Methods The study of population included patients enrolled in the PURSUIT trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) with known smoking status presenting with ischemic chest pain ≤24 hours and having either ischemic electrocardiographic changes without persistent ST-segment elevation or elevated creatine kinase MB levels. Patients were randomly assigned to receive a bolus and infusion of either eptifibatide or placebo in addition to standard therapy. The primary end point was a composite of death or nonfatal myocardial infarction within 30 days. Results of the 9406 patients with known smoking status, 2677 were current smokers, 3086 were former smokers, and 3643 were nonsmokers. Cigarette smokers had better 30-day outcomes (12.3%, 16.8%, and 15.4% for smokers, former smokers, and nonsmokers, respectively; P = .001). However, after adjusting for differences in baseline clinical variables, smoking status was not a predictor of 30-day outcome ( P = .45). There was a reduction in the composite end point overall with eptifibatide compared with placebo (14.3% vs 15.7%, P = .054) but no interaction between smoking status and treatment strategy ( P = .68). Conclusions Among patients with ACS without persistent ST-segment elevation, cigarette smokers had better short-term outcomes because of their more favorable clinical profile. Although prior studies have suggested that smokers more commonly have platelet-rich thrombi than nonsmokers, eptifibatide did not result in more improvement in their outcome compared with former smokers or nonsmokers.

Current Evidence For The Use Of Platelet Gpiib/iiia Receptor Inhibitors In Acute Coronary Syndromes

Current Evidence For The Use Of Platelet Gpiib/iiia Receptor Inhibitors In Acute Coronary Syndromes

Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II

<h2>Summary</h2><h3>Background</h3> Platelet-mediated thrombosis has been implicated in the development of ischaemic complications of percutaneous coronary intervention. We investigated whether inhibition of the platelet glycoprotein IIb/IIIa integrin with eptifibatide (Integrilin) could prevent such complications. <h3>Methods</h3> We undertook a double-blind, placebo-controlled trial at 82 centres in the USA, enrolling 4010 patients undergoing elective, urgent, or emergency coronary intervention. Patients were assigned one of three treatments: placebo (n=1328), a bolus of 135 μg/kg eptifibatide followed by an infusion of 0·5 μg kg⁻¹ min⁻¹ for 20–24 h (n=1349), or 135 μg/kg eptifibatide bolus with a 0·75 μg kg⁻¹ min⁻¹ infusion (n=1333). The coronary procedure was started within 10–60 min of the start of study treatment. The primary endpoint was the 30-day composite occurrence of death, myocardial infarction, unplanned surgical or repeat percutaneous revascularisation, or coronary stent implantation for abrupt closure (by intention to treat). The primary safety endpoint was major bleeding. <h3>Findings</h3> By 30 days, the composite endpoint had occurred in 151 (11·4%) patients in the placebo group compared with 124 (9·2%) in the 135/0·5 eptifibatide group (p=0·063) and 132 (9·9%) in the eptifibatide 135/0·75 group (p=0·22). By treatment-received analysis, the 135/0·5 regimen produced a significant reduction in the composite endpoint (11·6 <i>vs</i> 9·1%, p=0·035), but the 135/0·75 regimen produced a less substantial reduction (11·6 <i>vs</i> 10·0%, p=0·18). Eptifibatide treatment did not increase rates of major bleeding or transfusion. <h3>Interpretation</h3> In the 135/0·5 group, treatment with eptifibatide during coronary intervention reduced rates of early abrupt closure and ischaemic events at 30 days. Non-significant differences were seen with the 135/0·75 regimen. The doses studied thus appear to be at the low end of the efficacy-response curve. Further investigation to refine eptifibatide dosing during coronary intervention is warranted.