Clinical Investigations: Acute Ischemic Heart DiseaseFirst report of an intravenous and oral glycoprotein IIb/IIIa inhibitor (RPR 109891) in patients with recent acute coronary syndromes: Results of the TIMI 15A and 15B trials☆,☆☆,★
Section snippets
TIMI 15A
Ninety-three patients were enrolled over a 6-month period. Inclusion criteria were acute coronary syndrome ≤48 hours, age 18 to 75 years, creatinine clearance ≥50 mL/min, and ability to provide informed consent. Exclusion criteria were hemorrhagic risk, severe concomitant illness, active substance abuse, pregnancy/lactation, recent participation in another experimental protocol, current or prior thrombocytopenia, planned coronary artery bypass grafting (CABG) in ≤24 hours, low-molecular-weight
Patient population and treatments
Baseline characteristics are shown in Table I. Data are % of patients unless otherwise specified. MI, Myocardial infarction; PCI, percutaneousEmpty Cell TIMI 15A TIMI 15B All patients n 91 192 283 Age(y, mean ± SD) 55.4 ± 9.9 60.0 ± 10.8 58.5 Male 76 74 75 Prior MI 39 30 33 Prior CABG or PCI 12 32 26 Prior aspirin 68 83 78 Index event ST-elevation MI 28 26 25 Non-ST-elevation MI 25 25 25 Unstable angina without MI 47 49 48 Therapy of index event Fibrinolytic 13 15 14 PCI within 24 hours 19 17 16 Received adjunctive heparin 86 88 87
Discussion
In this first report of a single GP IIb/IIIa receptor inhibitor administered to patients in an intravenous followed by oral formulation, we observed a dose-dependent increase in plasma concentration, RO, and IPA with both intravenous and oral formulations of RPR 109891. Greater fluctuation and lower levels of IPA were seen with oral administration. Variability in the pharmacodynamic effect of short-acting oral GP IIb/IIIa inhibitors caused by a relatively low and variable bioavailability is
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Supported by a grant from Rhone-Poulenc Rorer, Collegeville.
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*Persons and institutions participating in TIMI 15A and 15B are listed in the Appendix.
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Reprint requests: Robert P. Giugliano, MD, TIMI Study Office, 333 Longwood Ave, Suite 402, Boston, MA 02115.E-mail: [email protected]