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Ugeskrift For Laeger Apr 2024Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended... (Review)
Review
Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended prophylactic low-dose acetylsalicylic acid (LDA). If new screening algorithms are implemented, LDA will be recommended to around 10% of pregnant women. The use of LDA may slightly increase the risk of minor bleeding disturbances. Otherwise, there is a lot of promising data regarding the safety of LDA use during pregnancy, as argued in this review.
Topics: Humans; Pre-Eclampsia; Pregnancy; Aspirin; Female; Platelet Aggregation Inhibitors
PubMed: 38704715
DOI: 10.61409/V10230682 -
European Journal of Pharmacology May 2021Aspirin is an old drug extracted from willow bark and is widely used for the prevention and treatment of cardiovascular diseases. Accumulating evidence has shown that... (Review)
Review
Aspirin is an old drug extracted from willow bark and is widely used for the prevention and treatment of cardiovascular diseases. Accumulating evidence has shown that aspirin use may significantly reduce the angiogenesis of cancer; however, the mechanism of the association between angiogenesis and aspirin is complex. Although COX-1 is widely known as a target of aspirin, several studies reveal other antiangiogenic targets of aspirin, such as angiotensin II, glucose transporter 1, heparanase, and matrix metalloproteinase. In addition, some data indicates that aspirin may produce antiangiogenic effects after acting in different cell types, such as endothelial cells, platelets, pericytes, and macrophages. In this review, we concentrate on research regarding the antiangiogenic effects of aspirin in cancer, and we discuss the molecular mechanisms of aspirin and its metabolites. Moreover, we discuss some mechanisms through which aspirin treatment may normalize existing blood vessels, including preventing the disintegration of endothelial adheres junctions and the recruitment of pericytes. We also address the antiangiogenic effects and the underlying mechanisms of aspirin derivatives, which are aimed at improving safety and efficacy.
Topics: Angiogenesis Inhibitors; Animals; Aspirin; Humans; Neoplasms; Neovascularization, Pathologic; Signal Transduction
PubMed: 33657423
DOI: 10.1016/j.ejphar.2021.173989 -
Contemporary Clinical Trials Jul 2023Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following... (Observational Study)
Observational Study
BACKGROUND
Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort.
METHODS
Descriptive statistics compared health characteristics of those consented to ASPREE-XT at their first post-trial baseline (XT01) to corresponding ASPREE baseline values, and to those not consented. Likelihood of an indication for aspirin was assessed in participants reporting aspirin use at XT01.
RESULTS
16,317 (93%) of the remaining and eligible 17,546 ASPREE participants were consented into ASPREE-XT; 14,894 completed XT01. Mean participant age had increased from 74.9 to 80.6 years. Overall health and physical function declined from the original ASPREE baseline; more participants were living alone, there was higher prevalence of chronic kidney disease, diabetes, and frailty, grip strength was lower and gait speed slower. Those not consented into ASPREE-XT were slightly older, and had lower cognitive scores and higher prevalence of age-related conditions than those who continued. 1015/11,717 (8.7%) participants without an apparent indication for aspirin reported using aspirin at XT01.
CONCLUSIONS
The ASPREE-XT cohort was slightly less healthy at the XT01 visit than at ASPREE trial initiation, and rates of aspirin use without indication were similar to ASPREE baseline. Participants will be followed long-term to investigate aspirin's potential legacy towards dementia and cancer prevention and explore determinants of healthy aging.
Topics: Humans; Aged; Aged, 80 and over; Aspirin; Double-Blind Method; Cognition
PubMed: 37196887
DOI: 10.1016/j.cct.2023.107231 -
PloS One 2023Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a...
Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a variety of vasoactive bioactive lipid metabolites during the inflammatory response and produce pro-resolving mediators (e.g., Lipoxin A4, LXA4) in cooperation with leukocytes and platelets to bring a halt to inflammation. Aspirin, used in a variety of cardiovascular and pro-thrombotic disorders (e.g., atherosclerosis, angina, preeclampsia), potently inhibits proinflammatory eicosanoid formation. Moreover, aspirin stimulates the synthesis of pro-resolving lipid mediators (SPM), so-called Aspirin-Triggered Lipoxins (ATL). We demonstrate that cytokines stimulated a time- and dose-dependent increase in PGI2 (6-ketoPGF1α) and PGE2 formation that is blocked by aspirin. Eicosanoid production was caused by cytokine-induced expression of cyclooxygenase-2 (COX-2). We also detected increased production of pro-resolving LXA4 in cytokine-stimulated endothelial cells. The R-enantiomer of LXA4, 15-epi-LXA4, was enhanced by aspirin, but only in the presence of cytokine challenge, indicating dependence on COX-2 expression. In contrast to previous reports, we detected arachidonate 5-lipoxygenase (ALOX5) mRNA expression and its cognate protein (5-lipoxygenase, 5-LOX), suggesting that endothelial cells possess the enzymatic machinery necessary to synthesize both pro-inflammatory and pro-resolving lipid mediators independent of added leukocytes or platelets. Finally, we observed that, endothelial cells produced LTB4 in the absence of leukocytes. These results indicate that endothelial cells produce both pro-inflammatory and pro-resolving lipid mediators in the absence of other cell types and aspirin exerts pleiotropic actions influencing both COX and LOX pathways.
Topics: Humans; Aspirin; Cyclooxygenase 2; Endothelial Cells; Lipoxins; Inflammation; Eicosanoids; Cytokines
PubMed: 37098090
DOI: 10.1371/journal.pone.0283163 -
Wiley Interdisciplinary Reviews.... Sep 2020Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in... (Review)
Review
Epidemiological data indicate that long-term low dose aspirin administration has a protective effect against the occurrence of colorectal cancer, both in sporadic and in hereditary forms of the disease. The mechanisms underlying this protective effect, however, are incompletely understood. The molecular events that lead to protection have been partly defined, but remain to be fully characterized. So far, however, approaches based on evolutionary dynamics have not been discussed much, but can potentially offer important insights. The aim of this review is to highlight this line of investigation and the results that have been obtained. A core observation in this respect is that aspirin has a direct negative impact on the growth dynamics of the cells, by influencing the kinetics of tumor cell division and death. We discuss the application of mathematical models to experimental data to quantify these parameter changes. We then describe further mathematical models that have been used to explore how these aspirin-mediated changes in kinetic parameters influence the probability of successful colony growth versus extinction, and how they affect the evolution of the tumor during aspirin administration. Finally, we discuss mathematical models that have been used to investigate the selective forces that can lead to the rise of mismatch-repair deficient cells in an inflammatory environment, and how this selection can be potentially altered through aspirin-mediated interventions. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Analytical and Computational Methods > Analytical Methods Analytical and Computational Methods > Computational Methods.
Topics: Aspirin; Cell Cycle Checkpoints; Cell Proliferation; Evolution, Molecular; Humans; Models, Theoretical; Neoplasms
PubMed: 32163237
DOI: 10.1002/wsbm.1487 -
Hematology. American Society of... Dec 2020Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient... (Review)
Review
Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient populations. Clinical research in the prevention and treatment of VTE has been a dynamic field of study, with investigations into various treatment modalities ranging from mechanical prophylaxis to the direct oral anticoagulants. Aspirin has long been an inexpensive cornerstone of arterial vascular disease therapy, but its role in the primary or secondary prophylaxis of VTE has been debated. Risk-benefit tradeoffs between aspirin and anticoagulants have changed, in part due to advances in surgical technique and postoperative care, and in part due to the development of safe, easy-to-use oral anticoagulants. We review the proposed mechanisms in which aspirin may act on venous thrombosis, the evidence for aspirin use in the primary and secondary prophylaxis of VTE, and the risk of bleeding with aspirin as compared with anticoagulation.
Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Hemorrhage; Humans; Male; Venous Thromboembolism
PubMed: 33275727
DOI: 10.1182/hematology.2020000150 -
Tissue & Cell Jun 2022Bone tissues are one of the most complex tissues in the body that regenerate and repair themselves spontaneously under the right physiological conditions. Within the... (Review)
Review
Bone tissues are one of the most complex tissues in the body that regenerate and repair themselves spontaneously under the right physiological conditions. Within the limitations of treating bone defects, mimicking tissue engineering through the recruitment of scaffolds, cell sources and growth factors, is strongly recommended. Aspirin is one of the non-steroidal anti-inflammatory drugs (NSAIDs) and has been used in clinical studies for many years due to its anti-coagulant effect. On the other hand, aspirin and other NSAIDs activate cytokines and some mediators in osteoclasts, osteoblasts and their progenitor cells in a defect area, thereby promoting bone regeneration. It also stimulates angiogenesis by increasing migration of endothelial cells and the newly developed vessels are of emergency in bone fracture repair. This review covers the role of aspirin in bone tissue engineering and also, highlights its chemical reactions, mechanisms, dosages, anti-microbial and angiogenesis activities.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bone Remodeling; Endothelial Cells; Osteogenesis; Tissue Engineering; Tissue Scaffolds
PubMed: 35180553
DOI: 10.1016/j.tice.2022.101753 -
International Journal of Cancer Mar 2021Aspirin has been associated with a reduced risk of colorectal and other selected digestive tract cancers, but the evidence for other neoplasms is still controversial. To... (Meta-Analysis)
Meta-Analysis
Aspirin has been associated with a reduced risk of colorectal and other selected digestive tract cancers, but the evidence for other neoplasms is still controversial. To provide an up-to-date quantification of the role of aspirin on lung, breast, endometrium, ovary, prostate, bladder, and kidney cancer, we conducted a systematic review and meta-analysis of all observational studies published up to March 2019. We estimated pooled relative risk (RR) of cancer or cancer death for regular aspirin use vs non-use by using random-effects models, and, whenever possible, we investigated dose- and duration-risk relations. A total of 148 studies were considered. Regular aspirin use was associated to a reduced risk of lung (RR = 0.88, 95% confidence interval [CI] = 0.79-0.98), breast (RR = 0.90, 95% CI = 0.85-0.95), endometrial (RR = 0.91, 95% CI = 0.84-0.98), ovarian (RR = 0.91, 95% CI = 0.85-0.97) and prostate (RR = 0.93, 95% CI = 0.89-0.96) cancer. However, for most neoplasms, nonsignificant risk reductions were reported in cohort and nested case-control studies and there was between-study heterogeneity. No association was reported for bladder and kidney cancer. No duration-risk relations were observed for most neoplasms, except for an inverse duration-risk relation for prostate cancer. The present meta-analysis confirms the absence of appreciable effect of regular aspirin use on cancers of the bladder and kidney and quantifies small and heterogeneous inverse associations for other cancers considered.
Topics: Aspirin; Humans; Neoplasms; Observational Studies as Topic
PubMed: 32984948
DOI: 10.1002/ijc.33311 -
Clinical Biochemistry Nov 2020Acetylsalicylic acid (ASA) or brand name Aspirin is a widely available medication used to relieve inflammation, fever and pain. It has also been frequently prescribed as... (Review)
Review
Acetylsalicylic acid (ASA) or brand name Aspirin is a widely available medication used to relieve inflammation, fever and pain. It has also been frequently prescribed as prevention for cardiovascular disease due to its anti-thrombotic qualities. However, ASA is also connected to increased internal bleeding, leading to concerns that this harmful side effect may outweigh its cardioprotective properties in some populations. In this review, we summarize data from several recent, large-scale clinical trials that put into the question the long-standing recommendations about prescribing ASA for primary cardiovascular disease. We also provide a detailed overview of the role of ASA in cancer, surgery and female reproductive health. Finally, we discuss the ASA prescription guidelines of several major medical organizations and suggest that this new evidence may lead to updates to these influential and longstanding recommendations.
Topics: Aspirin; Cardiovascular Diseases; Clinical Trials as Topic; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Treatment Outcome
PubMed: 32721423
DOI: 10.1016/j.clinbiochem.2020.07.003 -
Clinical Pharmacokinetics Apr 2022Aspirin is one of the most widely used medicines. Although aspirin is commonly utilized for the treatment of several medical conditions, its broadest uptake is for the... (Review)
Review
Aspirin is one of the most widely used medicines. Although aspirin is commonly utilized for the treatment of several medical conditions, its broadest uptake is for the prevention of recurrent ischemic events in patients with atherosclerotic disease. Its mechanism of action of inhibiting platelet activation via blockade of thromboxane A production is unique and is not covered by any other antiplatelet agents. While plain, uncoated, immediate-release aspirin is used in acute settings to help assure rapid absorption, enteric-coated aspirin formulations dominate current chronic use, particularly in North America, including for secondary prevention of cardiovascular events. The unmet needs with current aspirin formulations include a high risk of gastrointestinal (GI) adverse events with plain aspirin, which enteric-coated formulations are not able to overcome, and subject to erratic absorption leading to reduced drug bioavailability. These observations underscore the need for aspirin formulations with a more favorable safety and efficacy profile. Phospholipid-aspirin complex (PL-ASA) is a novel formulation designed to address these needs. It is associated with reduced local acute GI injury compared with plain aspirin, and predictable absorption resulting in more reliable platelet inhibition compared with enteric-coated tablets. This review explores the rationale and pharmacologic profile of PL-ASA intended to address the unmet needs for aspirin therapy.
Topics: Aspirin; Blood Platelets; Humans; Phospholipids; Platelet Aggregation Inhibitors; Tablets, Enteric-Coated
PubMed: 35060092
DOI: 10.1007/s40262-021-01090-2