Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis

• Published in: Handbook of experimental pharmacology Vol. 270; p. 103
• Main Authors: Olie, R H, van der Meijden, P E J, Spronk, H M H, Ten Cate, H
• Format: Journal Article
• Language: English
• Published: Germany 2022
• Subjects: Animals; Aspirin; Atherosclerosis - drug therapy; Atherosclerosis - prevention & control; Clopidogrel; Fibrinolytic Agents - therapeutic use; Humans; Platelet Aggregation Inhibitors - therapeutic use; Antiplatelet therapy; Anticoagulants; Aspirin; Atherosclerosis; Coagulation; Clopidogrel; Atherothrombosis; Platelets; Thrombosis
• ISSN: 0171-2004
• DOI: 10.1007/164_2020_357

Atherosclerosis is a multifactorial vascular disease that develops in the course of a lifetime. Numerous risk factors for atherosclerosis have been identified, mostly inflicting pro-inflammatory effects. Vessel injury, such as occurring during erosion or rupture of atherosclerotic lesions triggers blood coagulation, in attempt to maintain hemostasis (protect against bleeding). However, thrombo-inflammatory mechanisms may drive blood coagulation such that thrombosis develops, the key process underlying myocardial infarction and ischemic stroke (not due to embolization from the heart). In the blood coagulation system, platelets and coagulation proteins are both essential elements. Hyperreactivity of blood coagulation aggravates atherosclerosis in preclinical models. Pharmacologic inhibition of blood coagulation, either with platelet inhibitors, or better documented with anticoagulants, or both, limits the risk of thrombosis and may potentially reverse atherosclerosis burden, although the latter evidence is still based on animal experimentation.Patients at risk of atherothrombotic complications should receive a single antiplatelet agent (acetylsalicylic acid, ASA, or clopidogrel); those who survived an atherothrombotic event will be prescribed temporary dual antiplatelet therapy (ASA plus a P2Y12 inhibitor) in case of myocardial infarction (6-12 months), or stroke (<6 weeks), followed by a single antiplatelet agent indefinitely. High risk for thrombosis patients (such as those with peripheral artery disease) benefit from a combination of an anticoagulant and ASA. The price of gained efficacy is always increased risk of (major) bleeding; while tailoring therapy to individual needs may limit the risks to some extent, new generations of agents that target less critical elements of hemostasis and coagulation mechanisms are needed to maintain efficacy while reducing bleeding risks.