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Integrilin
Clinical Pharmacology
Integrilin
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.
| | 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.
| | 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. | |||
Generic Name: Eptifibatide
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