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All ASPIRIN SUMMARIES

ISSUE Conference 2022 Session 4

Conference 2022 : Session 4 : The place of aspirin in Gynaecology

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The place of aspirin in Gynaecology
Chairpersons Carlo Patrono (Italy) and Lina Badimon (Spain)

The Place of Antiplatelet Therapy in Obstetrics and Gynaecology Elisa Llurba (Spain)

Pre-eclampsia is an important complication of pregnancy that brings an 83% increase in severe maternal disease and has a 78% association with intrauterine growth restriction (IUGR)/prematurity and foetal hypoxia. It presents with high blood pressure and proteinuria. The condition is character- ised by endothelial dysfunction with:

  • Increased sensitivity to angiotensin II and norepinephrine
  • Cyclocxygenase-1 with decreased PG12/TXA2 and vasoconstriction
  • Increased endothelial-cell permeability and intravascular hypovolaemia
  • Platelet aggregation
  • An inflammatory response
  • Coagulation activation

There is immunological interaction (HLA-NK), trophoblastic invasion impairment (IFNỿ, VEGF, PIGF,NO), placental ischemia, an increase in trophoblast debris, Increased sFlt-1, decreased PIGF and increased cytokines. Aspirin helps at lots of different points including the immunological interactions, the vasoconstriction, platelet aggregation and inflammatory response.

In 1978 the first case report of the use of aspirin to prevent recurrent pre-eclampsia was published1 and in 19852 the first randomised controlled trial was performed using aspirin to help prevent pre-eclampsia with positive results. In 2010 a meta-analysis3 was performed showing a 10% reduction in pre-eclampsia rate and a further study4 showed that the timing of the intervention before 16 weeks was important. In 2018 a dose of 150mg as well as the timing of aspirin initiation was shown to be appropriate5.

As a result, NICE6 recommend the use of aspirin 75-150 mg daily in pregnant women at high-risk of pre-eclampsia from 12 weeks until birth. They define high risk as women with:

  • Hypertensive disease during a previous pregnancy
  • Chronic kidney disease
  • Autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome
  • Type 1 or 2 diabetes
  • Chronic hypertension6

NICE6 also recommend that women with more than one of the following moderate risk factors for pre-eclampsia take aspirin 75-150 mg from 12 weeks gestation until delivery:

  • First pregnancy
  • Age 40 years or older
  • Pregnancy interval of more than 10 years
  • Body mass index (BMI) of 35kg/m2 or more at time of first visit
  • Family history of pre-eclampsia
  • Multiple pregnancy6

Identifying at risk women is important for prevention and taking a thorough maternal history along with biophysical parameters such as blood pressure at the scan appointment helps to identify 85% of at-risk women.

The ASPRE7 trial compared aspirin 150 mg daily versus placebo in the pregnancies of 1610 women who were at high risk of preterm pre-eclampsia. The aspirin group had an 82% drop in the rate of early pre-eclampsia and a 62% drop in the rate of preterm pre-eclampsia making it a worthwhile intervention.

Data from the ASPRE and SPREE trials7,8 showed that aspirin also reduces the number of small for gestation age (SGA) neonates with a 40% reduction in SGA <37 weeks and a 73% reduction is SGA at <32 weeks.

Major improvements have helped to reduce maternal deaths in the UK with 200 deaths per 10,000 population in the 1950s, 100 in the 1970s, 19 in 2006-2008, 10 in 2009-2011 and 2 between 2012 and 20149. These improvements in obstetric care have been due to:

  • Fluid restricting management of pulmonary oedema
  • Management of severe hypertension
  • So4Mg-eclampsia
  • Timely delivery
  • Aspirin prophylaxis since 2010 in the UK

Aspirin is considered safe for women and their babies. Large cohort and case-control studies have reported that aspirin is not associated with an increase in risk of structural or developmental anomalies.

A study has shown that women on aspirin for other reasons improve their rates of pregnancy. As a result, a new randomised study is underway looking at different cardiovascular parameters before pregnancy and during pregnancy to see if aspirin can improve the cardiovascular state pre pregnancy and help women to get pregnant and to have a successful pregnancy.

In summary, pre-eclampsia is an important cause of maternal, foetal and neonatal morbidity and mortality. It still is one of the leading causes of maternal mortality and ASPRE has shown that using an algorithm to identify at risk women at the beginning of pregnancy and give aspirin at 150mg at night during the pregnancy reduced the rate of pre-term pre-eclampsia. There are still some controversies regarding whether aspirin could be used universally and if there are certain subgroups of women that will benefit from a combination of different drugs. Further studies to ascertain if aspirin will help to the reduce long-term effects of cardiovascular conditions during pregnancy are needed.

References

  1. Beaufils M, Donsemont R, Uzax S and Colau JC. Case report. Lancet, 2 (1978) p5.
  2. Beaufils M, Uzac S, Donsemont R and Colau JC. Prevention of pre-eclampsia by early antiplatelet therapy. Lancet. 1985 Apr 13:1(8433):840-2.
  3. Fox et al. BJOG 2010
  4. Bujold E Obs and Gynecol 2010
  5. Roberge AJOG 2018
  6. NICE guideline NG133 Hypertension in pregnancy: diagnosis and management. 2019. www.nice.org.uk/guidelines/ng133
  7. Rolnik DL, Wright D, Poon L et al. Aspirin versus placebo in pregnancies at high risk for preterm pre-eclampsia. N Engl J Med. 2017 Aug 17,377(7):613-622
  8. Tan MY, Wright D, Syngelaki A et al. Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combing maternal factors and biomarkers: results of SPREE. Ultrasound Obstet Gynecol. 2018 Jun;51(6):743-750.
  9. Shennan AH, Green M and Chappell LC. Maternal deaths in the UK: pre-eclampsia deaths are avoidable. Lancet. 2017 Feb 11 389 (10069); 582-584.

Round Table Discussion

Elisa Llurba (Spain), Carlo Patrono (Italy) and Lina Badimon (Spain).

It was agreed that aspirin is an inexpensive drug and there- fore the guidelines for aspirin in those at risk of pre-eclampsia are easily implemented globally. Work to look at how aspirin can help in the preparation of women for in vitro fertilisation is on-going and will be of increasing importance as women choose to become pregnant later in life. Cardiovascular dis- ease can appear in the fourth or fifth decade of life in women that suffered during the perinatal time. We need to prevent not only pre-eclampsia but also later cardiovascular disease in women.

The question of all pregnant women being treated with aspirin was raised and Dr Elisa Llurba replied that this needs considering as two scenarios. Firstly, in low- and middle-in- come countries that cannot perform screening giving aspirin to all pregnant women could be an option. However, in countries and settings where we can perform screening, it is better to identify women at risk for various reasons;

  • Women can be made aware of the risk of such complications and that aspirin lowers the risk but does not completely exclude it
  • Once identified these women can be followed up during pregnancy to ensure they are managed if they develop the pre-eclampsia
  • Compliance is always related to the sensation of the risk. Folic acid also recommended during pregnancy is only taken by 20% of pregnant women because they don’t feel they need it. If they are not aware of the risk, they are less likely to take aspirin.

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2022 Scientific Conference Session 4
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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

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