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Learn the pathophysiology of atherothrombosis and mechanisms by which aspirin, P2Y12 inhibitors and anticoagulants exert antithrombotic effect.
Describe key randomised clinical trials of antithrombotic therapy in patients with chronic coronary syndromes (CCS) that inform current practice.
Use recommendations in the 2019 European Society of Cardiology CCS guidelines to make evidence-based decisions regarding choice and duration of antithrombotic agent for patients with CCS.
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.
Pathophysiology and pharmacology of thrombosis
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 …
Contributors WAEP drafted the article under supervision of RFS, who edited and approved the final version.
Funding WAEP is supported by British Heart Foundation Clinical Research Training Fellowship no. FS/18/49/33752.
Competing interests RFS reports institutional research grants/support from AstraZeneca, GlyCardial Diagnostics and Thromboserin; consultancy fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Cytosorbents, GlyCardial Diagnostics, Haemonetics, Portola and Thromboserin; and honoraria from AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer and Medscape.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Commissioned; externally peer reviewed.
Data availability statement No data are available.
Author note References which include a * are considered to be key references.
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