John J. Young

Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban.

Background: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported. Methods/Results: We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition.Conclusion: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.

Therapeutic adjuncts for immediate transfer to the catheterization laboratory in patients with acute coronary syndromes.

Early coronary intervention in patients with non-ST-segment elevation myocardial infarction (MI) and unstable angina may be made safer and more efficacious with concomitant therapies, including glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparins. Stent placement has been shown to improve procedural success and reduce major in-hospital complications when compared with balloon angioplasty alone in patients with unstable angina. However, unstable angina remains a major hazard for adverse coronary events in long-term follow-up after elective stent placement. The currently available glycoprotein IIb/IIIa inhibitors-eptifibatide, tirofiban, and abciximab--have each been shown to reduce ischemic events before percutaneous coronary intervention when administered to patients presenting with non-ST-segment elevation acute coronary syndromes in large clinical trials. The adjunctive role of low-molecular-weight heparins in this scenario has been largely unexplored. Enoxaparin, when given before angiography or percutaneous coronary intervention, has been shown to be superior to unfractionated heparin in preventing major coronary events. In this review, an algorithm for treatment of non-ST-segment elevation acute coronary syndromes is presented and the current role of these newer adjunctive pharmacotherapies is explored. In the future, combinations of these agents may prove to be most beneficial in patients undergoing early percutaneous coronary intervention.

A Guide to Drug Use During Percutaneous Coronary Intervention

The past decade has seen major advances in adjunctive pharmacotherapy for percutaneous coronary intervention. Pharmacological therapeutic advances have resulted from a greater understanding of the pathophysiological mechanisms underlying platelet activation and aggregation, thrombin generation and thrombus formation. Specifically, refinements in the use of unfractionated heparin, developments in the use of low molecular weight heparins and direct antithrombin agents as well as improvement in both oral and parenteral adjunctive antiplatelet therapies have occurred and are reviewed herein.