Percutaneous Coronary Intervention: Adjunctive Pharmacology

Abstract

Percutaneous coronary intervention (PCI) promotes thrombosis by inducing extreme vascular injury. The concomitant presence of dysfunctional endothelium, vulnerable plaque, and endothelial erosion promotes further thrombotic risk. Platelet adhesion to newly exposed collagen and von Willebrand factor by specific receptors and binding of thrombin generated by tissue factor to protease-activated receptors (PARs) cause initial platelet activation. Following activation, adenosine diphosphate (ADP) is released from dense granules and thromboxane A₂ is generated by cyclooxygenase-1 (COX-1). Although both thromboxane A₂ and ADP amplify platelet activation and aggregation, continuous ADP-P2Y₁₂ receptor signaling is essential for sustained activation of the GPIIb/IIIa receptor and stable thrombus generation. Simultaneously, platelet activation exposes the phosphatidylserine surface providing binding sites for coagulation factors and the generation of thrombin. Thrombin converts fibrinogen to fibrin and activates factor XIII that cross-links the fibrin network, stabilizes the platelet-fibrin clot at the site of vascular injury, and impairs myocardial blood supply. Therefore, the rationale for antithrombotic therapy during and following PCI is to prevent thrombus formation within the target lesion and also in nontarget vessels by attenuating platelet activation and aggregation and arresting coagulation processes. Since clot formation involves multiple pathways including platelet activation and aggregation and coagulation, simultaneous blockade of these pathways is essential to prevent periprocedural and post-PCI ischemic event occurrences. Optimal inhibition of these pathways is essential for maximizing antithrombotic effects and minimizing bleeding risk and is critically dependent on individual patient risk.