OBJECTIVES: The goal of this study was to evaluate platelet function and to preliminarily assess the clinical safety of sequential treatment with tirofiban or eptifibatide followed by abciximab in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: An increasing number of acute coronary syndrome (ACS) patients are treated early with tirofiban or eptifibatide. Some later require PCI and may benefit from switching to abciximab, for which long-term benefits have been reported. METHODS: Fifty ACS patients planned for PCI were enrolled. Twenty-five patients received tirofiban followed by abciximab. Ten patients received eptifibatide followed by abciximab. Fifteen patients received only abciximab. All patients had blood samples drawn six times during the therapeutic course. Platelet function was evaluated by ADP- and TRAP-induced aggregation, flow cytometry analysis of fibrinogen binding and the cone and plate(let) analyzer, which tests shear rate-dependent platelet activation. RESULTS: Administered after tirofiban, abciximab caused a significant further decline in platelet function, as evidenced by all methods. Administered after eptifibatide, abciximab caused a significant further reduction in platelet function, as assessed by the cone and plate(let) analyzer and fibrinogen binding methods. The platelet inhibition achieved by the combination therapy was always greater than or equal to that achieved by abciximab alone. There were no major bleeding or severe thrombocytopenia episodes. Three of the 35 combination therapy patients and one of the 15 who received abciximab alone had minor bleeding. CONCLUSIONS: This is the first in vivo study of combination intravenous platelet glycoprotein IIb/IIIa inhibitor therapy. Administration of abciximab immediately after tirofiban or eptifibatide therapy effectively inhibits platelet function and appears to be safe.