Skip to content
  • Home
  • History
    • Introduction
    • The Aspirin Story
    • Timeline
    • Chemistry
  • Advisory Board
  • Awards
  • Conferences
  • Scientific Information
    • Guidelines
    • Disease Prevention
    • Aspirin Summaries
    • Aspirin Matters
  • News
  • Contact
Menu
  • Home
  • History
    • Introduction
    • The Aspirin Story
    • Timeline
    • Chemistry
  • Advisory Board
  • Awards
  • Conferences
  • Scientific Information
    • Guidelines
    • Disease Prevention
    • Aspirin Summaries
    • Aspirin Matters
  • News
  • Contact
Search
Close this search box.
All ASPIRIN SUMMARIES

ISSUE Conference 2022 Session 1

Conference 2022 : Session 1 : The place of aspirin in Cardiology

Table of Contents

Download PDF

The Role of Aspirin in the Current Therapeutic Armamentarium

125 years of aspirin-inspired research
Professor Carlo Patrono (Italy)

The past fifty years of aspirin were presented with a particular focus on the research leading to its utilisation as an antiplatelet medication and its important role in reducing cardiovascular events. Aspirin continues to keep the scientific community interested and has a class one A recommendation for patients with cardiovascular disease (CVD), in the acute setting and long-term secondary prevention.

Aspirin has a unique mechanism of action because it permanently inactivates platelet cyclooxygenase (COX)-1 through selective acetylation of a single serine residue near the catalytic site of the enzyme. COX-1 normally catalyses the conversion of arachidonic acid to prostaglandin (PG) G2, but when the enzyme is acetylated by aspirin it loses its catalytic activity and thromboxane synthesis is suppressed. The so calle “aspirin dilemma” was that aspirin inhibits both the synthesis of a pro-aggregatory and vasoconstrictor substance, thromboxane (TX)A2, and of an endogenous antiplatelet and valodilator autacoid, i.e., prostacyclin (PGI2).

In 1982 Carlo Patrono and his group published work, in healthy subjects, demonstrating log-linear inhibition of platelet TXA2 production after single oral doses of aspirin in the range 10-100 mg.1 Moreover, repeated daily administration of aspirin gave a cumulative antiplatelet response with a 30-mg dose resulting in complete suppression of platelet COX-1 activity.1 Later work showed that the cumulative inactivation of platelet COX-1 by daily dosing of aspirin enhanced its potency 8-fold, with saturable inhibition of TXA2 production at doses <<100 mg.2 Garret FitzGerald also published work showing that both prostacyclin and thromboxane are differentially suppressed with cumulative dosing of aspirin in healthy subjects3.

These findings led a trio of brilliant investigators at the University of Oxford, Sir Richard Peto, Sir Rory Collins and Professor Peter Sleight to launch a very large, placebo- controlled, randomized trial, ISIS-2.4 This trial, published in 1988, established low-dose aspirin as a life-saving drug in the setting of an acute myocardial infarction (MI).

In 2020 Tom Meade, Jan van Gijn, Lars Wallentin and Bo Norrving shared the IAF Senior Science Award for their pioneer trials of low-dose aspirin (30 to 75 mg daily) for the prevention of coronary and cerebrovascular events.

Aspirin has now been shown to be effective in preventing serious vascular events at low doses in a variety of vascular disorders: hypertension (75 mg), stable angina (75 mg), unstable angina (75 mg), acute MI (160 mg), TIA and ischemic stroke (50-75 mg), severe carotid artery stenosis (81mg) and acute ischemic stroke (160 mg).5 Work by Colin Baigent, who coordinated the Antithrombotic Trialists Collaboration, through a metanalysis of aspirin trials in high-risk patients, showed no evidence of a dose-response relationship for the antithrombotic effect of aspirin, consistent with saturability of platelet COX-1 inhibition at low aspirin doses.6

Blood platelets have a multifaceted role in human physiology and pathophysiology including:

  • Primary haemostasis: vascular integrity, cessation of bleeding
  • Tissue repair
  • Angiogenesis
  • Innate and adaptive immunity
  • Embryonic development
  • Arterial thrombosis
  • Inflammation
  • Atherosclerosis
  • Cancer metastasis

In addition to its role in Cardiology, interest continues to thrive in many of the above areas for aspirin and disease prevention.

Aspirin is now in its 125th year and continues to be a cornerstone of antiplatelet therapy for cardiovascular prevention. Newer antiplatelet agents are also available but have not convincingly demonstrated better safety or efficacy. Combination therapy, with low-dose aspirin and other antiplatelet, e.g., P2Y12 receptor blocker or anticoagulant drug, is now used when a more effective antithrombotic strategy is required for those at higher risk.7

References

  1. Patrignani P, Filabozzi P and Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J.Clin.Invest 1982; 69; 1366-1372
  2. Patrono C, Ciabattoni G, Patrignani P et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation 1985 72(6):1177-84
  3. FitzGerald GA, Oates JA, Hawiger R et al. endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983;71(3):676-688
  4. ISIS-2 Collaborative Group Randomised trial of intravenous streptokinase, oral aspirin both or neither among 17187 cases of suspected acute myocardial infarction: ISIS-2 Lancet 1988 332;(8607) 349-360
  5. Patrono C, Baigent C, Hirsh J et al. Antiplatelet drugs: American College of Chest Physicians Evidence – Based Clinical Practice Guidelines (8th Edition) Chest 2008 ;133 (6Suppl):199s-233S
  6. Antithrombotic Trialists’ Collaboration Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction and stroke in high-risk patients. BMJ 2002; 324:71-86
  7. Patrono C. Fifty years with aspirin and platelets. Br J Pharmacol 2022; 1-19DOI; 10.1111/bph.15966

 

The place of aspirin in Cardiology: Treatment vs Prevention
Professor J Michael Gaziano (USA)

The role of aspirin in acute treatment and secondary prevention has been widely studied with over 400 large scale trials that looked at the use of aspirin in acute settings and among individuals with a variety of manifestations of atherosclerotic disease, testing the hypothesis that platelet inhibition with aspirin will lower the risk in acute CVD settings and subsequently among those with known atherosclerotic disease (prior MI or stoke, CAD, TIA, or peripheral artery disease).

The acute treatment trial ISIS-2 changed clinical practice by showing that 162 mg of aspirin given at the time of an acute MI resulted in a 23% reduction of death or MI, an effect that persisted for years. The absolute benefit was 2.4% and the NNT= approximately 40. There was also no apparent bleeding risk giving a favourable risk benefit ratio1.

In secondary prevention, the risk of a second CVD event is very high with a 40% chance of a second event over 10 years and a lifetime risk of 80%. In this setting, aspirin has a clear role. Here the 25% relative risk reducing intervention of aspirin results in the secondary prevention scenario having a NNT = 10.

The assessment of the benefits of aspirin in primary prevention are more complicated because absolute risks of vascular events are lower than in secondary prevention while complication rates are comparable. For example, with a 10- year risk of a CVD event of 1%, a 25% relative risk reduction strategy would result in an estimated NNT = 400. Therefore, the study of aspirin in primary prevention requires much larger studies for longer periods of time than secondary prevention studies.

Fifteen large trials have explored the role of aspirin in primary prevention among those with no known CVD. Aspirin has a lesser effect in this group and much longer trials are needed to see a benefit. In the Physician’s Health Study2 with 11037 taking aspirin and 11034 taking placebo a 44% reduction in first MI was found in the aspirin group.

Whilst the biology of the first CVD event is likely to be the same as a second event, the observed efficacy of aspirin in primary prevention trials appears to be affected by lower compliance with the study medication over the longer time frame of these trials. As time has gone on it has been harder to do primary prevention trails and get the same efficacy as the early trails, because the overall events are less now due to an improvement in CVD risk reduction strategies.

Several primary prevention trials were presented in 2018 and although there has been a lot of discussion over the results:

  • The ASCEND study showed that aspirin works the same in people with diabetes as those without3
  • ASPREE showed that aspirin does not prevent the combined outcome of dementia, death and disability4
  • ARRIVE was not successful in assessing the impact of aspirin in those at moderate risk and had attempted to recruit a higher risk group of patients.5

Doing placebo-controlled trials of aspirin is challenging in the 21st century. In general, results from the three trials are consistent with the previous primary studies that demonstrate aspirin’s ability to lower the risk of first major CVD event with more impact on MI and to increase the risk of bleeding dominated by GI bleeding with no difference in fatal bleeding.

Compliance issues have impacted the ability to demonstrate the efficacy of low-dose aspirin in the primary prevention setting but the per protocol analysis, of people who maintained the aspirin therapy, in ARRIVE is similar to the Physicians Health study undertaken in the 1990s. Interestingly, when these new results were pooled in meta- analysis the overall data didn’t change.
Clinically, there are three potential strategies for improving the benefit/risk profile of aspirin in primary prevention:

  • Improve risk assessment and optimize the aspirin regimen
  • Include the potential impact of low-dose aspirin on non- vascular outcomes (e.g., colorectal cancer (CRC)
  • Improve the safety profile of low-dose aspirin by increasing the use of gastroprotectant agents e.g., PPIs particularly in the elderly.

In summary, low-dose aspirin is universally recommended for acute treatment and secondary prevention of CVD events, it is also generally recommended for those at higher risk with diabetes. It can also be considered in primary prevention for those with a high risk of CVD. The use of aspirin remains a decision that should involve a discussion between a clinician and a patient given the need to weigh the CV and cancer benefits against the bleeding risk, patient’s preferences, costs and other factors.

References

  1. ISIS-2 Collaborative group Randomised trial of intravenous streptokinase, oral aspirin, both , or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1998; 332 (8607) 349-360
  2. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med. 1989 Jul 20;321(3):129-35. doi: 10.1056/NEJM198907203210301. PMID: 2664509
  3. Bowman L, Mafham M, Stevens W, Haynes R, Aung T, Chen F, Buck G, Collins R, Armitage J; ASCEND Study Collaborative Group. ASCEND: A Study of Cardiovascular Events iN Diabetes: Characteristics of a randomized trial of aspirin and of omega-3 fatty acid supplementation in 15,480 people with diabetes. Am Heart J. 2018 Apr;198:135-144. doi: 10.1016/j. ahj.2017.12.006. Epub 2017 Dec 24. PMID: 29653635; PMCID: PMC5971211
  4. McNeil j, Nelson M, Woods R et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018; 379:1519- 1528
  5. Gaziano JM, Brotons C, Coppolecchia R et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised double-blind, placebo-controlled trial. Lancet 2018 392 (10152); 1036-1046

Round Table Discussion

Professors’ Junbo Ge (China), Jean-Phillipe Collet (France), Carlo Patrono (Italy), J Michael Gaziano (USA), Bianca Rocca (Italy) and Gemma Vilahur (Spain) Aspirin is regularly used in the Chinese adult population, but the dosage used is smaller in the elderly and in low weight women where 25mg or 50 mg doses are selected instead of the usual 75-100 mg daily dose recommended for those of a more standard weight. Helicobacter pylori has been identified as an important factor in the Chinese population contributing to bleeding risk with aspirin and efforts are being made to investigate and treat this infection. Factors such as age or having comorbidities and other medications e.g., anticoagulants for atrial fibrillation can complicate the picture. It is important to find ways to identify the thrombus prone population and the use of calcium scores may help with this.

From France a view was raised that the distinction between primary and secondary CVD prevention was artificial and that instead a linear increased risk should be considered with the same risk scale used to define aspirin strategy. Getting the balance between risk and benefit right can be complex and better use of tools is required to do this accurately, for example using imaging to identify high risk patients.

Other discussion looked at how CVD risk, as a whole, is better controlled now than in the 1990s, for example, lipid control; blood pressure control; and aggressive management of familial hypercholesterolaemia.

Health care providers need to identify those patients most likely to benefit from aspirin therapy by utilising risk assessment tools and empowering patients with the knowledge of aspirins preventative effects.

Back to top

SHARE THIS ARTICLE

Facebook
Twitter
LinkedIn
2022 Scientific Conference Session 1
Download the full summary as a PDF document.
Download PDF

Connect with us

Sign up to be part of the aspirin community and be the first to receive latest information.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Have something to say about aspirin?

Contact Us Here
Footer Logo
  • Terms & Conditions
  • Branding Guidelines
  • Privacy
  • Cookie Policy
  • Disclaimer
  • Terms & Conditions
  • Branding Guidelines
  • Privacy
  • Cookie Policy
  • Disclaimer
TwitterLinkedin

Copyright © 2023 Aspirin Foundation

Website by mtc.

Have something to say about aspirin?

Please fill in the form below and we will contact you with further information.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Djp

Daniel José Piñeiro

ASSOCIATE
Name
Daniel José Piñeiro
Academic Affiliations:
Full Professor of Medicine, Universidad de Buenos Aires, Argentina Trustee, Board of Trustees, American College of Cardiology
Professional Setting:
My academic experience includes more than 40 years as a practicing medical doctor, teacher, and researcher. I have fulfilled these appointments in settings of vital social engagement and impact, most notably at the Hospital de Clínicas “José de San Martín” of the Universidad de Buenos Aires, a public hospital with high academic recognition. Additionally, I currently hold the position of Full Professor of Medicine at that same University.
Academic Activities:
  • International Meetings Participations: 180
  • Books-Editor: 1
  • Books Chapters: 39
  • Refereed Full Articles: 118 (listed in Pubmed: 29)
  • Refereed Abstracts: 221
  • Editorial Boards: 10
Profesional Associations:
  • 2005 President, Sociedad Argentina de Cardiología.
  • 2011-2013 President, Inter-American Society of Cardiology.
  • 2011-2013 Member (ex-officio), Board of Directors, World Heart Federation
  • 2017-2018 Member (at large), Board of Directors, World Heart Federation
  • 2018-2021 Trustee, Board of Trustees, American College of Cardiology
Return to Scientific Advisory Board
Chia

John Chia

Name
John Chia MBBS (Spore), MRCP (UK), FAMS (Spore)
Academic Affiliations:

Adjunct Associate Professor DUKE-NUS Graduate Medical School,
Consultant Oncologist Curie Oncology Singapore,
Visiting Consultant National Cancer Centre Singapore.

Discipline:

Medical Oncology

Scientific Interests:
  • Aspirin as adjuvant therapy in established cancers
  • Adoptive T cell therapy and Dendritic cell vaccines in the treatment of solid tumors
  • Clinical Trial Design and Management
Declaration of Conflicts of Interest:

In the past 3 years, I have received consultant fees from Tessa Therapeutics, Aslan Pharmaceuticals, Novartis, and AstraZeneca.

I received grant support for investigator-initiated research from:

  • National Medical Research Council Singapore
  • Bayer AG

I hold shares in:  Roche, BMS, AstraZeneca, Incyte, Teva Pharmaceuticals, Trillium Therapeutics, Compugen, Arrowhead pharmaceuticals, Emergex, QuantumDx and Halozyme Therapeutics

Return to Scientific Advisory Board
Badimon

Lina Badimon

Name
Lina Badimon BSc, PharmD, PhD, FESC, FAHA
Academic Affiliations:
Director of the Cardiovascular Science Program (ICCC) at the Hospital Santa Creu and San Pau, IIB-Sant Pau; CIBER CV. Director of the Cardiovascular Research Chair of the Autonomous University of Barcelona and Director of the UNESCO Chair in Biomedical Sciences Training and Research.
Discipline:
Pharmacology, Cardiovascular Disease
Scientific Interests:
Cardio-metabolic diseases, thrombosis, atherosclerosis and ischemic heart disease
Declaration of Conflicts of Interest:

I received consultant and speakers fees from Amgen, AstraZeneca, Bayer, Lilly and Sanofi.

    Return to Scientific Advisory Board
    Ge

    Junbo Ge

    Name

    Junbo Ge

    Ge Junbo, male, was born in Wulian, Shandong province on Nov. 8, 1962. He is the member of Chinese Academy of Sciences, professor and doctoral supervisor. He received his doctor’s degree of Medicine from German Mayence University in 1993 and now works as the director for Shanghai Institute of Cardiovascular Disease and the Center for Stem Cells and Tissue Engineering, Fudan University. He is also the designate chairman of the Cardiovascular Disease Branch of Chinese Medical Association, council member of the Cardiovascular Angiography and Interventions Association, international consultant of the American Heart Association. In Dec. 2013, he was appointed as the vice president of Tongji University.

    Prof. Ge has been engaged in clinical and scientific research work of cardiovascular disease since 1987, and his research area covers the pathogenesis of coronary heart disease, early diagnosis and treatment plan optimization.

    Return to Scientific Advisory Board
    Langley

    Ruth Langley

    Name
    Ruth Langley PhD, FRCP
    Academic Affiliations:
    Professor of Oncology and Clinical Trials, MRC Programme Leader and Chair of the Cancer Group, MRC Clinical Trials Unit at UCL, honorary consultant in medical oncology at the Brighton and Sussex University Hospital.
    Discipline:
    Medical oncologist; trialist
    Scientific Interests:
    • Aspirin
    • Gastro-oesophageal malignancy
    • Transdermal oestrogen in the treatment of prostate cancer
    • Trials methodology
    Declaration of Conflicts of Interest:
    Has received honorarium from Bayer
    Return to Scientific Advisory Board
    Chan

    Andrew T Chan

    Name
    Andrew T. Chan MD, MPH
    Academic Affiliations:
    Chief, Clinical and Translational Epidemiology Unit, Vice Chair, Division of Gastroenterology, Massachusetts General Hospital, Boston, Co-leader, Cancer Epidemiology Program, Dana-Farber/Harvard Cancer Center, Boston.
    Discipline:
    Gastroenterology
    Scientific Interests:
    • The role of aspirin in the prevention of colorectal cancer and other cancers
    • The role of the gut microbiome in colorectal cancer and other chronic gastrointestinal diseases, including inflammatory bowel disease and diverticulitis
    • The role of diet and lifestyle in colorectal cancer and other chronic gastrointestinal cancers
    Declaration of Conflicts of Interest:

    AACR Honors Dr. Andrew T. Chan With 2019 AACR-Waun Ki Hong Award

    Click here to find the press release.

    I received consultant Bayer and Pfizer, Inc.

    I received grant support for investigator-initiated research from:

    • National Institutes of Health
    • National Cancer Institute
    • Crohn’s and Colitis Foundation
    • Bayer AG
    Return to Scientific Advisory Board
    Gaziano

    Mike Gaziano

    Name
    J Michael Gaziano MD, MPH
    Academic Affiliations:

    Professor of Medicine, Harvard Medical School; Chief Division of Aging, Brigham and Women’s Hospital; Director of Preventive Cardiology and Director of Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System.
    Discipline: Cardiology and Epidemiology

    Scientific Interests:
    I am a chronic disease epidemiologist with a particular interest in the roles that individual lifestyle choices (diet, exercise, smoking), metabolic factors (obesity, high cholesterol, and hypertension), and biochemical and genetic markers play on the risk of cardiovascular disease and other chronic illnesses. Also, of interest is the impact that vascular disease has on other organ systems, including cognitive dysfunction and renal disease. I have an interest in the design of large-scale trials and observational studies nested in large health care systems using big data analytic techniques.
    Declaration of Conflicts of Interest:

    I received consultant and speaker fees Bayer.

    I received grant support as a principal investigator or co-investigator for research from the VA, DOD, NIH, Merck and Kowa.

    Return to Scientific Advisory Board
    Rothwell

    Peter Rothwell

    PAST – CHAIR
    Name

    Peter M. Rothwell PhD, MD, FRCP, FMedSci

    Academic Affiliations:
    • Action Research Chair of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford;
    • Founding Director, Wolfson Centre for Prevention of Stroke and Dementia, University of Oxford;
    • Wellcome Trust Senior Investigator;
    • Emeritus NIHR Senior Investigator;
    • Theme Leader, Stroke and Vascular Dementia, NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford
    Discipline:
    Neurology and Stroke Medicine
    Scientific Interests:
    • Risks and benefits of aspirin;
    • Primary and secondary prevention of stroke;
    • Effects of blood pressure on the brain.
    Declaration of Conflicts of Interest:
    I received consultant and speakers fees from Bayer AG.
    CarloPatrono

    Carlo Patrono

    CHAIR
    Name
    Carlo Patrono MD, FESC, FRCP
    Academic Affiliations:
    Adjunct Professor of Pharmacology at the Catholic University School of Medicine in Rome (Italy) and at the Perelman School of Medicine of the University of Pennsylvania in Philadelphia (USA).
    Discipline:
    Clinical Pharmacology
    Scientific Interests:
    • Studying platelet activation and inhibition in diabetes mellitus
    • Studying platelet activation and inhibition in myeloproliferative neoplasms
    • Investigating the mechanism of action of low-dose aspirin in preventing colorectal cancer
    Declaration of Conflicts of Interest:

    I received consultant and speakers fees from Acticor Biotech,  Amgen,  Bayer, GlaxoSmithKline,  Tremeau,  Zambon.

    I received grant support for investigator-initiated research from:

    • AIFA (Italian Drug Agency)
    • Bayer AG
    • Cancer Research UK
    • European Commission, FP6 and FP7 Programmes

      Return to Scientific Advisory Board

      Have something to say about aspirin?

      We would like to hear from you and have a chat, and maybe feature you on our podcast. Please fill in the form below and we will contact you with further information.

      This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.