Antithrombotic therapy for patients with chronic coronary syndromes
William A. Parker, Robert F. Storey
Abstract
### Learning objectives Globally, much morbidity and premature mortality arises from coronary artery disease (CAD). Coronary artery atherothrombosis is the dominant cause of acute coronary syndromes (ACS), including spontaneous myocardial infarction (MI) and unstable angina. Those with chronic coronary syndromes (CCS), including stable CAD or an ACS event >1 year ago, are at ongoing atherothrombotic risk.1 Modifiable or partially modifiable risk factors such as hypercholesterolaemia, diabetes mellitus (DM), hypertension and smoking, and unmodifiable factors such as age and chronic kidney disease (CKD), can initiate and accelerate coronary atherosclerosis.2 Understanding the pathophysiology of atherothrombosis has helped to identify and exploit therapeutic targets. In 2019, the European Society of Cardiology (ESC) published new guidelines on the management of CCS, including antithrombotic therapy.3 In this review, we evaluate the pathophysiology and pharmacology of atherothrombosis, highlight up-to-date evidence from randomised controlled trials (RCTs), and discuss the content and application of the the ESC 2019 CCS guidelines. ### The thrombotic response While atherosclerotic plaques are thrombogenic even when intact, thrombosis is typically triggered by plaque rupture/erosion, allowing blood constituents to make contact with prothrombotic factors such as collagen.4 Platelet activation is central to atherothrombosis (figure 1).5 Collagen activates platelets via glycoprotein VI receptors. Subsequently, arachidonic acid is converted to prostaglandin H2 by the enzyme cyclo-oxygenase (COX) 1, and then, by thromboxane A2 (TXA2) synthase, to TXA2, which further enhances platelet activation via thromboxane-receptor-α.6 Intracellular granules fuse with the …