Clinical Research
Clinical Trial
Correlates of Bleeding Events Among Moderate- to High-Risk Patients Undergoing Percutaneous Coronary Intervention and Treated With Eptifibatide: Observations From the PROTECT–TIMI-30 Trial

https://doi.org/10.1016/j.jacc.2005.09.080Get rights and content
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Objectives

We aimed to identify correlates of Thrombolysis In Mycocardial Infarction (TIMI) major/minor bleeding among eptifibatide-treated patients undergoing percutaneous coronary intervention (PCI).

Background

Evaluation of bleeding predictors among patients treated with glycoprotein IIb/IIIa receptor inhibition might aid in the identification of targets to reduce bleeding risk.

Methods

Data were analyzed from 567 moderate- to high-risk PCI patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) treated with eptifibatide/reduced-dose unfractionated heparin or eptifibatide/reduced-dose enoxaparin enrolled in the Randomized Trial to Evaluate the Relative Protection Against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia Among Anti-Platelet and Anti-Thrombotic Agents–Thrombolysis In Myocardial Infarction-30 (PROTECT–TIMI-30).

Results

The incidence of significant bleeding was 3.2% with a median time to event of 7.0 h after the first eptifibatide bolus. Increased age was the only independent correlate of bleeding events. Among patients with reduced creatinine clearance (CrCl), lack of adjustment of the maintenance infusion for CrCl ≤50 ml/min occurred frequently (15 of 33 patients, or 45%) and was associated with a high rate of bleeding (20%). The association of CrCl with bleeding appeared to be largely mediated by the incorporation of age in the estimation of CrCl. Patient gender, Cr, weight, and the peak activated clotting time were not associated with bleeding.

Conclusions

Among NSTEACS PCI patients treated with eptifibatide, increased age was a significant correlate of bleeding events and appeared to explain the association between low CrCl and bleeding. The more widespread use of CrCl or other estimates of renal function over Cr may lead to more appropriate dose adjustments of eptifibatide.

Abbreviations and Acronyms

ACS
acute coronary syndrome
ACT
activated clotting time
Cr
creatinine
CrCl
creatinine clearance
GFR
glomerular filtration rate
GPIIb/IIIa
glycoprotein IIb/IIIa receptor
NSTEACS
non–ST-segment elevation acute coronary syndrome
PCI
percutaneous coronary intervention
UFH
unfractionated heparin

Cited by (0)

Supported in part by a grant from Millennium Pharmaceuticals, Cambridge, Massachusetts, and Schering-Plough Research Institute, Kenilworth, New Jersey.

1

Dr. Cohen has received grant support from the Medicines Company, Millennium Pharmaceuticals, and Schering-Plough.

2

Dr. Peterson has received grant support from Schering-Plough and Millennium Pharmaceuticals.

3

Dr. Herrmann has received research funding from Millennium Pharmaceuticals and has served as a consultant for Millennium Pharmaceuticals.

4

Dr. Palabrica is an employee of Millennium Pharmaceuticals.

5

Dr. Gibson has received grant support and honoraria and has served as a consultant for the Medicines Company, Millennium Pharmaceuticals, and Schering-Plough.