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Integrilin

Clinical Pharmacology
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Clinical Pharmacology

The primary endpoint of the ESPRIT study was the composite of death, MI, urgent target vessel revascularization (UTVR) and "bailout" to open label eptifibatide due to a thrombotic complication of PCI (TBO) (e.g., visible thrombus, "no reflow", or abrupt closure) at 48 hours. MI, UTVR and TBO were evaluated by a blinded Clinical Events Committee.

As shown in Table 5, the incidence of the primary endpoint and selected secondary endpoints was significantly reduced in patients who received eptifibatide. A treatment benefit in patients who received eptifibatide was seen by 48 hours and at the end of the 30-day observation period.

Table 5
Clinical Events in the ESPRIT Study
Placebo
(n=1024)
Eptifibatide
180/2.0/180
(n=1040)
Relative Risk
(95% CI)
p-Value
Death, MI, Urgent Target Vessel Revascularization,
or Thrombotic "Bailout"
48 Hours (primary endpoint)
108 (10.5%) 69 (6.6%) 0.629 (0.471, 0.840) 0.0015
30 Days
120 (11.7%) 78 (7.5%) 0.640 (0.488, 0.840) 0.0011
Death, MI, or Urgent Target
Vessel Revascularization
48 Hours
95 (9.3%) 62 (6.0%) 0.643 (0.472, 0.875) 0.0045
30 Days (key secondary endpoint)
107 (10.4%) 71 (6.8%) 0.653 (0.490, 0.871) 0.0034
Death or MI
48 Hours
94 (9.2%) 57 (5.5%) 0.597 (0.435, 0.820) 0.0013
30 Days
104 (10.2%) 66 (6.3%) 0.625 (0.465, 0.840) 0.0016

The need for thrombotic "bailout" was significantly reduced with eptifibatide at 48 hours (2.1% for placebo, 1.0% for eptifibatide; p=0.029). Consistent with previous studies of GP IIb/IIIa inhibitors, most of the benefit achieved acutely with eptifibatide was in the reduction of MI. Eptifibatide reduced the occurrence of MI at 48 hours from 9.0% for placebo to 5.4% (p=0.0015) and maintained that effect with significance at 30 days.

Follow-up (12 month) mortality data were available for 2024 patients (1017 on eptifibatide) enrolled in the ESPRIT trial (98.1% of the initial enrollment). Twelve-month clinical event data were available for 1964 patients (988 on eptifibatide) representing 95.2% of the initial enrollment. As shown in Table 6, the treatment effect of eptifibatide seen at 48 hours and 30 days appeared preserved at 6 months and 1 year. Most of the benefit was in reduction of MI.

Table 6
Clinical Events at 6 months and 1 year in the ESPRIT Study
Placebo
(n=1024)
Eptifibatide
180/2.0/180

(n=1040)
Hazard Ratio
(95% CI)
Death, MI, or Target
Vessel Revascularization
6 Months
187 (18.5%) 146 (14.3%) 0.744 (0.599, 0.924)
1 Year
222 (22.1%) 178 (17.5%) 0.762 (0.626, 0.929)
Death, MI
6 Months
117 (11.5%) 77 (7.4%) 0.631 (0.473, 0.841)
1 Year
126 (12.4%) 83 (8.0%) 0.630 (0.478, 0.832)
Percentages are Kaplan-Meier event rates.
Brand Name: Integrilin
Generic Name: Eptifibatide
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