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During the past 30 years, several developments have occurred in the antiplatelet field, including the role of aspirin in primary prevention of atherosclerotic cardiovascular disease. There have been several attempts to develop antiplatelet drugs more effective and safer than aspirin and a shift in emphasis from efficacy to safety, advocating aspirin-free antiplatelet regimens after percutaneous coronary intervention. Evidence supporting a chemopreventive effect of low-dose aspirin against colorectal (and other digestive tract) cancer has also strengthened. The aim of this article is to revisit the role of aspirin in the prevention of atherothrombosis across the cardiovascular risk continuum, in view of developments in the antiplatelet field. The review will offer a clinical perspective on aspirin's mechanism of action, pharmacokinetics, and pharmacodynamics. This will be followed by a detailed discussion of its clinical efficacy and safety., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-TXB2 (U-TXM), a stable metabolite reflecting the whole-body TXA2 biosynthesis, is reduced by ∼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation and is enhanced in patients with diabetes. This study assessed whether U-TXM is associated with the risk of future serious vascular events or revascularizations (SVE-R), major bleeding, or cancer in patients with diabetes., Methods: The U-TXM was measured pre-randomization to aspirin or placebo in 5948 people with type 1 or 2 diabetes and no cardiovascular disease, in the ASCEND trial. Associations between log U-TXM and SVE-R (n = 618), major bleed (n = 206), and cancer (n = 700) during 6.6 years of follow-up were investigated by Cox regression; comparisons of these associations with the effects of randomization to aspirin were made., Results: Higher U-TXM was associated with older age, female sex, current smoking, type 2 diabetes, higher body size, urinary albumin/creatinine ratio of ≥3 mg/mmol, and higher estimated glomerular filtration rate. After adjustment for these, U-TXM was marginally statistically significantly associated with SVE-R and major bleed but not cancer [hazard ratios per 1 SD higher log U-TXM (95% confidence interval): 1.09 (1.00-1.18), 1.16 (1.01-1.34), and 1.06 (0.98-1.14)]. The hazard ratio was similar to that implied by the clinical effects of randomization to aspirin for SVE-R but not for major bleed., Conclusions: The U-TXM was log-linearly independently associated with SVE-R in diabetes. This is consistent with the involvement of platelet TXA2 in diabetic atherothrombosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: R.V. received consulting or lecturing fees from Abbott Vascular, Amgen, Medtronic and Terumo, outside the submitted work. C.P. received consultant and speaker fees from AbbVie, Acticor Biotech, Amgen, Bayer, Eli Lilly, and Tremeau, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK and European Commission; he chaired the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest G.L. received consultant and speaker fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis, and grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service, and Italian Minister of Education, University and Research. G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She reports personal fees for speaker bureau from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi and Novartis, outside the submitted work. C.P. received consultant and speaker fees from AbbVie, Acticor Biotech, Amgen, Bayer, Eli Lilly, and Tremeau, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK and European Commission; he chaired the Scientific Advisory Board of the International Aspirin Foundation, outside the submitted work.

Competing Interests: Conflict of interest M.V. reports personal fees for speaker bureau and/or consulting in Advisory Board from Astra Zeneca, Kalos Medical, Menarini Int, Novartis Pharma, Novo Nordisk, Sanofi and Zentiva outside of the present work. C.P. received personal consultant and speaker fees from AbbVie, Acticor Biotech, Amgen, Bayer, Eli Lilly, and Tremeau, and grant support to his Institution for investigator-initiated research from Bayer AG and Cancer Research UK, outside the present work.

Competing Interests: Conflict of interest R.V. received speaker fees from Abbott Vascular, Amgen, and Terumo, outside the submitted work. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest R.V. received speaker’s fees from Abbott Vascular, Amgen and Terumo, outside the submitted work. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service, and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service, and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of Interest: All authors declare no conflict of interest for this contribution.

Competing Interests: Conflict of interest: Dr Vergallo received speaker fees from Abbott Vascular and Terumo, outside the submitted work. Prof. Carlo Patrono received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service, and Italian Minister of Education, University and Research. She is currently involved in the Research Programmes of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted, as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gastroprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, overall risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults., Competing Interests: Conflict of interest: The authors declare that none received specific funding in relation to the work: ‘Acute, periprocedural and longterm antithrombotic therapy in older adults: 2022 Update by the ESC Working Group on Thrombosis’ by Felicita Andreotti, Tobias Geisler, Jean-Philippe Collet, Bruna Gigante, Diana A Gorog, Sigrun Halvorsen, Gregory YH Lip, Joao Morais, Eliano Pio Navarese, Carlo Patrono, Bianca Rocca, Andrea Rubboli, Dirk Sibbing, Robert F. Storey, Freek W.A. Verheugt, and Gemma Vilahur., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflict of interest: M.V. reports personal fees for speaker bureau and/or consulting in Advisory Board from Amarin, Amgen, Astra Zeneca, Kalos Medical, Menarini Int, Novartis Pharma, Novo Nordisk, outside the submitted work. C.P. reports personal fees from Acticor Biotech, personal fees from Amgen, personal fees from Bayer, personal fees from GlaxoSmithKline, personal fees from Tremeau, personal fees from Zambon, grants from AIFA (Italian Drug Agency), grants from European Commission, other from Scientific Advisory Board of the International Aspirin Foundation, outside the submitted work.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programmes of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service, and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, and Zambon and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: R.V. received speaker fees from Abbott Vascular and Terumo. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, Tremeau, Zambon, and grant support (to the institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: M.V. reports personal fees for speaker bureau and/or consulting in Advisory Board from Amarin, Amgen, Astra Zeneca, Kalos Medical, Menarini Int, Novartis Pharma, Novo Nordisk, outside the submitted work. C.P. reports personal fees from Acticor Biotech, personal fees from Amgen, personal fees from Bayer, personal fees from GlaxoSmithKline, personal fees from Tremeau, personal fees from Zambon, grants from AIFA (Italian Drug Agency), grants from European Commission, other from Scientific Advisory Board of the International Aspirin Foundation, outside the submitted work.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, Tremeau, Zambon, and grant support (to the institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

Competing Interests: Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. She received personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi and Novartis. C.P. received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.