Drug of the Week - Aspirin

Presentation describing the storied history, mechanisms of action and historical vs. contemporary research of acetylsalicylic acid, known more readily around the world as aspirin.

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1. Dr. Robert Ferris Drug of the Week: ASPIRIN

2. Acetylsalicylic acid (ASA)

3. Acetylsalicylic acid (ASA ) (as an analgesic)

4. Dr. Sir John Robert Vane

5. Mechanism of action discovered by Sir John Robert Vane (the honorific of “Dr.” is no longer used in knighthood, in contrast to military honours), along with two other researchers studying aspirin’s effect on the knee joints of dogs This discovery Sir Vane the Nobel Prize in Physiology or Medicine However, salicylate-containing plants have been used for their analgesic and anti-inflammatory effects for thousands of years, most notably the bark of the willow tree Records of such uses can be traced to antiquity in Sumer, Egypt and the writings of Hippocrates

6. Willow

7. In 1853 chemist Charles Frédéric Gerhardt acetylated salicylic acid, creating ASA By 1897 Bayer was mass-producing the drug in tablet form, as opposed to the previously-used powder, marketed as “aspirin for the first time Over the next few decades the medication became so ubiquitous that the name “aspirin” entered the common vernacular, and is now the accepted generic name

8. In the latter half of the 20 th century aspirin began to lose popularity as an analgesic, with the development of novel NSAIDs (which, unlike aspirin, are reversible in their mechanisms of action) as well as, notably, paracetamol However, aspirin was simultaneously being investigated for a range of entirely new applications

9. Antiplatelet effects

10. Physicians’ Health Study I Randomized, double-blind, fixed sample trial where 22,071 American physicians took 32 5mg mane every 2/7 incidence of cardiovascular events measured vs. placebo Halted 3 years early due to apparent overwhelming benefit; 44% reduction in MI risk

11. However... Study design included not a single woman! US physician cohort in the mid-1980s consisted largely of white, upper-socioeconomic class participants, all over the age of 40 years Lifestyle of the day among such groups may have placed them in higher risk group for MI than the general public, which may confound results (conjecture)

12. Contemporary Research ARRIVE trial (2018): No significant reduction in risk of major cardiovascular events lower-than-expected incidence across all participants, attributing greater importance to lifestyle + other preventative measures ASCEND trial (2018): reduced risk of first vascular events in diabetic patients, but at the cost of increased incidence of hemorrhagic events requiring hospitalisation no absolute benefit ASPREE trial (2018): no survival benefit in elderly (>70y/o) non-comorbid patients increased mortality in aspirin group, though these are attributed primarily to cancers; no causative evidence

13. Conclusions Evidence for use in secondary prevention is well-supported No established benefit in primary prevention in patients without known comorbidities/risk factors Still an effective adjunct, which is cheap and easily accessible

14. References ‘Aspirin’, Wikipedia , accessed at https://en.wikipedia.org/wiki/Aspirin on 12/02/2021 Clark J., Bryant C. (2020) ‘Aspirin: The Wonder Drug’, Stuff You Should Know podcast Curtis E., Fuggle N. et al. (2019) ‘Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis’, Drugs & Aging 36: 25-44 Moncada S., Ferreira S., Vane J. (1975) ‘Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint’, European Journal of Pharmacology 31(2): 250-260 Pardutz A., Schoenen J. (2010)’ NSAIDs in the Acute Treatment of Migraine: A Review of Clinical and Experimental Data’, Pharmaceuticals 3(6): 1966-1987 Connelly D. (2014) ‘A history of aspirin’, Clinical Pharmacist 6(7), accessed at https://www.pharmaceutical-journal.com/news-and-analysis/infographics/a-history-of-aspirin/20066661.article?firstPass=false on 12/02/2021

15. References (contd.) Steering Committee of the Physicians' Health Study Research Group (1989) ‘Final Report on the Aspirin Component of the Ongoing Physicians' Health Study’, New England Journal of Medicine 321:129-135 Jackson G. (2019), ‘The female problem: how male bias in medical trials ruined women's health’, The Guardian Online, accessed at https://www.theguardian.com/lifeandstyle/2019/nov/13/the-female-problem-male-bias-in-medical-trials on 12/02/2021 Kuehn B. (2018), ‘Aspirin for Primary Prevention Takes a Hit With New Trial Results’, Circulation 138(23) Gaziano M., Brotons C. et al. (2018) ‘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’, The Lancet 392(10152): 1036-1046 ASCEND Study Collaborative Group (2018), ‘Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus’, New England Journal of Medicine 379: 1529-1539 McNeil J., Nelson M. et al. (2018) ‘Effect of Aspirin on All-Cause Mortality in the Healthy Elderly’, New England Journal of Medicine 379: 1519-1528

16. References (contd.) Byrne R., Colleran R. (2020), ‘Aspirin for secondary prevention of cardiovascular disease’, The Lancet 395(10235): 1462-1463 Gargiulo G., Windecker S. et al. (2016) ‘A Critical Appraisal of Aspirin in Secondary Prevention: Is Less More?’, Circulation 134(23) Côté E. (2015) ‘Clinical Approach to Arrhythmias’, accessed at https://www.vin.com/apputil/content/defaultadv1.aspx?id=7259356&pid=14365&print=1 on 12/02/2021 Richardson M. (2018) ‘What Are the Different Types of Stroke and How Do They Affect the Brain?’, BrainFacts.org , accessed at https://www.brainfacts.org/diseases-and-disorders/injury/2018/what-are-the-different-types-of-stroke-and-how-do-they-affect-the-brain-111918 on 12/02/2021 Lloyd D. (2020) ‘What happens during a heart attack?’, Parkview Health, accessed at https://www.parkview.com/community/dashboard/what-happens-during-a-heart-attack on 12/02/2021 ‘Physicians' Health Study’, ClinicalTrials.gov , accessed at https://clinicaltrials.gov/ct2/show/NCT00000500 on 12/02/2021