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Integrilin
Clinical Pharmacology
Integrilin
Patients were randomized to either placebo, eptifibatide 180 µg/kg bolus followed by a 2.0 µg/kg/min infusion (180/2.0), or eptifibatide 180 µg/kg bolus followed by a 1.3 µg/kg/min infusion (180/1.3). The infusion was continued for 72 hours, until hospital discharge, or until the time of coronary artery bypass grafting (CABG), whichever occurred first, except that if PCI was performed, the eptifibatide infusion was continued for 24 hours after the procedure, allowing for a duration of infusion up to 96 hours.
The lower-infusion-rate arm was stopped after the first interim analysis when the two active-treatment arms appeared to have the same incidence of bleeding.
Patient age ranged from 20 to 94 (mean 63) years, and 65% were male. The patients were 89% Caucasian, 6% Hispanic, and 5% Black, recruited in the United States and Canada (40%), Western Europe (39%), Eastern Europe (16%), and Latin America (5%).
This was a "real world" study; each patient was managed according to the usual standards of the investigational site; frequencies of angiography, PCI, and CABG therefore differed widely from site to site and from country to country. Of the patients in PURSUIT, 13% were managed with PCI during drug infusion, of whom 50% received intracoronary stents; 87% were managed medically (without PCI during drug infusion).
The majority of patients received aspirin (75-325 mg once daily). Heparin was administered intravenously or subcutaneously, at the physician's discretion, most commonly as an intravenous bolus of 5000 U followed by a continuous infusion of 1000 U/h. For patients weighing less than 70 kg, the recommended heparin bolus dose was 60 U/kg followed by a continuous infusion of 12 U/kg/h. A target aPTT of 50-70 seconds was recommended. A total of 1250 patients underwent PCI within 72 hours after randomization, in which case they received intravenous heparin to maintain an activated clotting time (ACT) of 300-350 seconds.
The primary endpoint of the study was the occurrence of death from any cause or new myocardial infarction (MI) (evaluated by a blinded Clinical Endpoints Committee) within 30 days of randomization.
Compared to placebo, eptifibatide administered as a 180 µg/kg bolus followed by a 2.0 µg/kg/min infusion significantly (p=0.042) reduced the incidence of endpoint events (see Table 2). The reduction in the incidence of endpoint events in patients receiving eptifibatide was evident early during treatment, and this reduction was maintained through at least 30 days (see Figure 1). Table 2 also shows the incidence of the components of the primary endpoint, death (whether or not preceded by an MI) and new MI in surviving patients at 30 days.
| Death or MI | Placebo (n = 4739) n (%) | Eptifibatide (180/2.0) (n = 4722) n (%) | p-value |
| 3 days | 359 (7.6%) | 279 (5.9%) | 0.001 |
| 7 days | 552 (11.6%) | 477 (10.1%) | 0.016 |
| 30 days | |||
| Death or MI | 745 (15.7%) | 672 (14.2%) | 0.042 |
| (Primary Endpoint) | |||
| Death | 177 (3.7%) | 165 (3.5%) | |
| Nonfatal MI | 568 (12.0%) | 507 (10.7%) | |
Generic Name: Eptifibatide
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