November 1, 1996Circulation110 citations
View Full PaperEffects of Integrelin, a Platelet Glycoprotein IIb/IIIa Receptor Antagonist, in Unstable Angina
Key Result
High-dose intravenous Integrelin significantly reduced the number (0.24 vs 1.0 episodes, P<0.05) and duration (8.41 vs 26.2 minutes, P=0.01) of Holter ischemic events compared with aspirin.
Key Points
- The aim is to evaluate the effect of Integrelin on the frequency and duration of ischemic episodes in patients with unstable angina.
- 227 patients were randomized to receive either oral aspirin with placebo Integrelin or varying doses of Integrelin with placebo aspirin.
- Patients underwent Holter monitoring for ischemic events for 24 to 72 hours.
- Platelet aggregation was measured in a subset of patients.
- High-dose Integrelin group had 0.24 ischemic episodes lasting 8.41 minutes, compared to the aspirin group with 1.0 episodes lasting 26.2 minutes (P < .05).
- There was no rebound ischemia after withdrawal of Integrelin.
- Integrelin rapidly inhibited platelet aggregation in a dose-dependent manner without significant bleeding differences between groups.
Study Design
Type
RCT (n=227)
Blinding
Placebo-controlled
Randomization
Randomized
Structured PICO
Does eptifibatide reduce the frequency and duration of Holter ischemia in patients with unstable angina compared to aspirin?
P
Population
227 patients with unstable angina receiving intravenous heparin and standard ischemic therapy, monitored with Holter for 24 to 72 hours.
I
Intervention
Eptifibatide (low-dose: 45 mcg/kg bolus followed by 0.5 mcg/kg/min continuous infusion; or high-dose: 90 mcg/kg bolus followed by 1.0 mcg/kg/min constant infusion) and placebo aspirin, added to intravenous heparin and standard ischemic therapy for 24 to 72 hours
C
Comparator
Oral aspirin and placebo eptifibatide, added to intravenous heparin and standard ischemic therapy
O
Outcome
Frequency and duration of Holter ischemia over 24 hours of study drug infusionsurrogate
Intravenous eptifibatide added to heparin significantly reduces the number and duration of ischemic events in unstable angina compared to aspirin.
Main Result
Absolute Event Rate: 0.24% vs 1%
p-value: p=< .05
Limitations
- The number of clinical events was small
Abstract
BACKGROUND: Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina. METHODS AND RESULTS: Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms. CONCLUSIONS: Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.