Platelet glycoprotein IIb/IIIa inhibitors have been extensively studied in the treatment of patients with
ischemic heart disease. Data regarding the use of these agents in the absence of concomitant intravenous
heparin have been conflicting. We sought to determine, using propensity analysis, whether the benefit of
eptifibatide, a IIb/IIIa inhibitor, in the treatment of
acute coronary syndromes is affected by the concurrent administration of
heparin. By trial design, patients were randomized to either
eptifibatide or placebo, whereas use of intravenous
heparin was left to the discretion of treating physicians. The effect of
eptifibatide on the 30-day composite end point of death or
myocardial infarction was studied in patients who received
heparin and those who did not. Propensity analysis methods were used to control for confounding and presumed selection biases. Among 5,576 patients who were receiving
heparin when the bolus dose of the study
drug was administered,
eptifibatide was associated with a reduced composite end point rate (13%) compared with that of placebo (14.5% vs 16.6%, p = 0.03). In contrast, among 1,441 patients who were not receiving
heparin, there was no difference in 30-day event rates with
eptifibatide compared with placebo (13.7% vs 13.1%, p > 0.7). After a propensity score for use of
heparin was developed, however, use of
heparin did not affect the reduced risk associated with
eptifibatide (adjusted relative risk [RR] for
heparin-
eptifibatide interaction term 0.90, 95% confidence interval [CI] 0.61 to 1.32, p > 0.5), but the propensity for
heparin use was a strong predictor of events (adjusted RR 1.76, 95% CI 1.42 to 2.17, p < 0.001). The use of
eptifibatide independently predicted a lower risk of events (adjusted RR 0.31, 95% CI 0.10 to 0.93, p = 0.04). Thus, the apparent positive impact of
heparin on the benefits of
eptifibatide therapy was largely due to confounding and bias.