New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism

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Abstract

The antithrombotic action of aspirin has long been recognized. Aspirin inhibits platelet function through irreversible inhibition of cyclooxygenase (COX) activity. Until recently, aspirin has been mainly used for primary and secondary prevention of arterial antithrombotic events. The aim of this study was to review the literature with regard to the various mechanisms of the newly discovered effects of aspirin in the prevention of the initiation and development of venous thrombosis. For this purpose, we used relevant data from the latest numerous scientific studies, including review articles, original research articles, double-blinded randomized controlled trials, a prospective combined analysis, a meta-analysis of randomized trials, evidence-based clinical practice guidelines, and multicenter studies. Aspirin is used in the prevention of venous thromboembolism (VTE), especially the prevention of recurrent VTE in patients with unprovoked VTE who were treated with vitamin K antagonists (VKAs) or with non-vitamin K antagonist oral anticoagulants (NOACs). Numerous studies have shown that aspirin reduces the rate of recurrent VTE in patients, following cessation of VKAs or NOACs. Furthermore, low doses of aspirin are suitable for long-term therapy in patients recovering from orthopedic or other surgeries. Aspirin is indicated for the primary and secondary prevention as well as the treatment of cardiovascular diseases, including acute coronary syndrome, myocardial infarction, peripheral artery disease, acute ischemic stroke, and transient ischemic attack (especially in atrial fibrillation or mechanical heart valves). Aspirin can prevent or treat recurrent unprovoked VTEs as well as VTEs occurring after various surgeries or in patients with malignant disease. Recent trials have suggested that the long-term use of low-dose aspirin is effective not only in the prevention and treatment of arterial thrombosis but also in the prevention and treatment of VTE. Compared with VKAs and NOACs, aspirin has a reduced risk of bleeding.

Most cited references 55

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Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.

M D Silverstein, J A Heit, D Mohr … (1998)

The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.

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Neutrophil extracellular trap (NET) impact on deep vein thrombosis.

Tobias Fuchs, Alexander Brill, Denisa D. Wagner (2012)

Deep vein thrombosis (DVT) is a major health problem that requires improved prophylaxis and treatment. Inflammatory conditions such as infection, cancer, and autoimmune diseases are risk factors for DVT. We and others have recently shown that extracellular DNA fibers produced in inflammation and known as neutrophil extracellular traps (NETs) contribute to experimental DVT. NETs stimulate thrombus formation and coagulation and are abundant in thrombi in animal models of DVT. It appears that, in addition to fibrin and von Willebrand factor, NETs represent a third thrombus scaffold. Here, we review how NETs stimulate thrombosis and discuss known and potential interactions of NETs with endothelium, platelets, red blood cells, and coagulation factors and how NETs could influence thrombolysis. We propose that drugs that inhibit NET formation or facilitate NET degradation may prevent or treat DVT.

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New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events

Ymer Mekaj, Agon Y Mekaj, Shkelzen B Duci … (2015)

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs.

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Author and article information

Journal

Journal ID (nlm-ta): Ther Clin Risk Manag

Journal ID (iso-abbrev): Ther Clin Risk Manag

Journal ID (publisher-id): Therapeutics and Clinical Risk Management

Title: Therapeutics and Clinical Risk Management

Publisher: Dove Medical Press

ISSN (Print): 1176-6336

ISSN (Electronic): 1178-203X

Publication date Collection: 2015

Publication date (Electronic): 24 September 2015

Volume: 11

Pages: 1449-1456

Affiliations

[1 ]Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo

[2 ]Department of Hemostasis and Thrombosis, National Blood Transfusion Center of Kosovo, University of Prishtina, Prishtina, Kosovo

[3 ]Clinic of Neurosurgery, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo

Author notes

Correspondence: Agon Y Mekaj, Clinic of Neurosurgery, Faculty of Medicine, University of Prishtina, Rrethi i Spitalit pn, Prishtina 10000, Kosovo, Tel +377 44 373 545, Email agon.mekaj@ 123456uni-pr.edu

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Publisher ID: tcrm-11-1449

DOI: 10.2147/TCRM.S92222

PMC ID: 4590672

PubMed ID: 26445544

SO-VID: 903846fe-c6e7-4ec9-980b-31a02044e875

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The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

New insights into the mechanisms of action of aspirin and its use in the prevention and treatment of arterial and venous thromboembolism

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Abstract

Most cited references 55

Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.

Neutrophil extracellular trap (NET) impact on deep vein thrombosis.

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events

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