Antiplatelet and antithrombin strategies in acute coronary syndrome: state-of-the-art review.

Refai Showkathali,Arun Natarajan

doi:10.2174/157340312803217193

Abstract

Antiplatelet and antithrombotic agents significantly alter the clinical course of patients with acute coronary syndrome (ACS) and hence form the bedrock of the management pathway of this closely related continuum of coronary pathologies. The contemporary therapeutic armamentarium for the treatment of ACS now reflects the many technical and pharmacological advances that took place over the last two decades. In the original 1996 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of acute myocardial infarction, only one antiplatelet agent (Aspirin) and one anticoagulant (unfractionated heparin) were recommended as class I therapies. Since then many newer agents have been developed and approved for routine clinical use in ACS patients. Recent research has focussed on improving efficacy on one hand and reducing bleeding complications on the other. This review focuses on the mechanism, efficacy, safety profile and clinical trial evidence of P2 Y12 receptor antagonist antiplatelet agents, glycoprotein IIb/IIIa receptor inhibitors (GPI), protease-activated receptor-1 (PAR-1) inhibitors, thrombin inhibitor bivalirudin and Factor Xa inhibitors fondaparinaux and rivaroxaban.

Highlights

Acute coronary syndromes (ACS), which include STsegment elevation myocardial infarction (STEMI), non-STsegment elevation myocardial infarction (NSTEMI) and unstable angina (UA), present a unique challenge to clinicians because of the high rate of mortality and morbidity associated with these conditions
This review focuses on the mechanism, efficacy, safety profile and clinical trial evidence of a) the P2Y12 receptor antagonists clopidogrel, prasugrel, ticagrelor and cangrelor, b) platelet glycoprotein IIb/IIIa receptor inhibitors (GPI), c) thrombin inhibitor bivalirudin and d) Factor Xa (FXa) antagonists- subcutaneous fondaparinux and oral rivaroxaban
In this study ischaemic cardiovascular events or cardiovascular death occurred in 16.5% of the patients treated with clopidogrel and aspirin therapy compared to 18.8% of the patients treated with aspirin alone, over a 3-12 months period (RR, 0.86; 95% CI, 0.79 to 0.94; P

Summary

Introduction

Acute coronary syndromes (ACS), which include STsegment elevation myocardial infarction (STEMI), non-STsegment elevation myocardial infarction (NSTEMI) and unstable angina (UA), present a unique challenge to clinicians because of the high rate of mortality and morbidity associated with these conditions. ACS occurs after the rupture of an inflamed atherosclerotic plaque, which exposes prothrombotic contents of the vascular matrix to flowing blood. Following plaque rupture, circulating platelets adhere to, and are activated by the exposed components of the vascular matrix. Tissue factor is exposed to plasma after plaque rupture, initiating the thrombotic cascade via its interaction with coagulation factor VII. Thrombin (vide infra) serves to amplify the response to the injury by further activation of platelets. These interactions result in the assembly of the prothrombinase complex on the surface of activated platelets and the generation of large amounts of thrombin that catalyzes the production of fibrin and cause the clinical manifestations of thrombosis and ACS [1]. In the original 1996 American College of Cardiology/American Heart Association

Objectives

Findings

Conclusion