Aspirin — History, Pharmacology & Modern Evidence

Aspirin in prepared form
Aspirin — prepared form, typical clinical or supplement presentation.
Aspirin body-systems response
Body systems responding to Aspirin — therapeutic pathways through affected tissue and bloodstream.
Aspirin active compounds at the cellular level
Aspirin at the cellular level — active compounds interacting with target cells.
🔥 Interactive Visualization Inflammation — fire the cascade and watch it resolve Follow injury through prostaglandins and leukotrienes to swelling — then watch omega-3-derived resolvins actively switch it off, and see what an NSAID really trades away. Launch → ⛓️ Interactive Visualization How Blood Clots — and how thinners stop it Build a platelet plug, weave a fibrin mesh, then watch aspirin, warfarin and a DOAC each break a different step — with a live INR. Launch →

Table of Contents

  1. Deep-Dive Articles
  2. A Brief History of Aspirin
  3. How Aspirin Works: A Quick Pharmacology Primer
  4. Dose Ranges in Trials and Guidelines
  5. Key Research Papers
  6. Featured Videos

Aspirin (acetylsalicylic acid, ASA) is, in the words of a 2017 history review, “now the most commonly used drug in the world” (PubMed). Pure acetylsalicylic acid was first prepared on 10 August 1897 in the pharmaceutical laboratory of a German company, and the drug was marketed in 1899 (PubMed). How it works was first explained in Vane's 1971 report that aspirin-like drugs inhibit prostaglandin synthesis (doi); in 1982 Vane shared the Nobel Prize in Physiology or Medicine with Bergström and Samuelsson “for their discoveries concerning prostaglandins and related biologically active substances” (NobelPrize.org).

Aspirin is studied in cardiology, oncology and nephrology. In people who already have occlusive vascular disease, the 2009 Antithrombotic Trialists' meta-analysis described low-dose aspirin as of “definite and substantial net benefit for many”, with reductions of about a fifth in total stroke and in coronary events (PubMed). In the 1988 ISIS-2 trial in suspected acute myocardial infarction, aspirin reduced 5-week vascular mortality (9.4% vs 11.8% with placebo tablets) (PubMed); what guidelines and health services state about aspirin during a suspected heart attack is set out under Dose Ranges in Trials and Guidelines below. Twenty-year follow-up of five randomised trials found that aspirin taken for several years at doses of at least 75 mg daily reduced long-term colorectal cancer incidence and mortality (PubMed). Aspirin also increases bleeding: in the six primary-prevention trials of the 2009 meta-analysis, major gastrointestinal and extracranial bleeds were 0.10% vs 0.07% per year and haemorrhagic stroke 0.04% vs 0.03% per year, and the authors called aspirin's net value in primary prevention uncertain (PubMed). In 2022 the US Preventive Services Task Force recommended against starting low-dose aspirin for primary prevention in adults 60 or older (PubMed). Effects on the kidneys are covered on the Aspirin & The Kidneys page.

Deep-Dive Articles

Aspirin Health Benefits

An overview of the research on aspirin's uses: cardiovascular protection, anti-inflammatory action, pain and fever, colorectal cancer, pre-eclampsia prevention, migraine and cluster headache, and research in dementia and diabetes. Also covers dosing forms and pharmacology, the USPSTF 2022 primary-prevention statement, and contraindications and cautions.

Aspirin for Heart Attack Prevention

The cardiovascular trial evidence: the ISIS-2 acute MI trial (1988), the Physicians' Health Study (1989), the Antithrombotic Trialists' Collaboration meta-analyses, and the 2018 primary-prevention trials (ARRIVE, ASCEND, ASPREE), with the USPSTF 2022 and ACC/AHA 2019 statements. Also covers what guidelines and health services state about aspirin during a suspected heart attack, dual antiplatelet therapy after stents, aspirin resistance, and the doses and formulations studied.

Aspirin for Stroke Prevention

The trial evidence on aspirin in acute ischemic stroke, prevention after stroke or TIA, and primary prevention. Covers the IST and CAST 1997 trials, the CHANCE and POINT dual antiplatelet trials, trials and the 2023 guideline comparing aspirin with anticoagulants in atrial fibrillation, and the measured increase in hemorrhagic stroke.

Aspirin & The Kidneys

The renal-physiology side of NSAID use: prostaglandin-mediated afferent arteriole vasodilation, acute kidney injury, analgesic nephropathy and papillary necrosis, the classic "triple whammy" of NSAID + ACE inhibitor + diuretic, considerations in chronic kidney disease and dialysis patients, and whether low-dose 81 mg carries meaningful renal risk.

Aspirin & Cancer Prevention

The colorectal cancer research: observational evidence from the Nurses' Health Study, randomized trial follow-up by Rothwell and colleagues, the CAPP2 Lynch syndrome trial, and the Add-Aspirin adjuvant cancer trial. Also covers the USPSTF's 2016 recommendation and its 2022 update, and research on esophageal, gastric, pancreatic and other cancers.

Aspirin Side Effects, Risks & Contraindications

The full risk profile: gastrointestinal bleeding and peptic ulcer disease, hemorrhagic stroke, Reye's syndrome in children and adolescents, tinnitus and salicylate toxicity, aspirin-exacerbated respiratory disease (Samter's triad), drug interactions with anticoagulants and SSRIs, pregnancy considerations, and perioperative management.

Glycine and Aspirin Metabolism: The Salicyluric Acid Pathway

The biochemistry of how the body clears aspirin: hydrolysis to salicylic acid and conjugation with glycine by the mitochondrial GLYAT enzyme to form salicyluric acid, a route that saturates as the dose rises. Covers the 1990 overdose studies that found lower plasma glycine in overdose patients, the Reye's syndrome connection, GLYAT genetic variants and collagen-rich food sources of glycine, and what is still unknown about whether glycine supply limits the pathway.

A Brief History of Aspirin

Aspirin's story runs from willow bark, which a 2017 review traces back more than 3,500 years as a pain reliever and antipyretic (PubMed), and the Reverend Edward Stone's 1763 report to the Royal Society on willow bark in the cure of agues (doi), to the first preparation of pure acetylsalicylic acid at a German company in 1897. Credit for that step is disputed: the long-standing account names the chemist Hoffmann, while Eichengrün wrote in 1949 that he had instructed Hoffmann to make the compound, and a 2000 reappraisal concluded that the most reasonable conclusion is that Eichengrün was telling the truth (PubMed). The story then runs to Vane's 1971 report on how aspirin works (doi). The fuller story is told in the dedicated History article.

How Aspirin Works: A Quick Pharmacology Primer

  1. Cyclooxygenase (COX) inhibition. The cyclooxygenase enzymes COX-1 and COX-2 convert arachidonic acid to prostaglandin G2 and then H2, which is converted into prostanoids including prostacyclin, prostaglandin E2 and thromboxane A2 (PubMed). Aspirin acetylates COX-1 at serine-529 and COX-2 at serine-516 (PubMed). The acetylation is irreversible; nucleated cells can make new enzyme within 4–6 hours (PubMed).
  2. Platelet COX-1 silencing. A 2026 review states that once-daily low-dose aspirin (75–100 mg) completely and permanently inactivates COX-1 in platelets, suppressing thromboxane A2-dependent platelet activation. Anucleate platelets have limited capacity to make new protein and live 7–10 days in humans, with an estimated 10–12% of circulating platelets newly formed each day, so the effect long outlasts aspirin's half-life of about 20 minutes (PubMed).
  3. COX-2 and higher doses. Low-dose aspirin selectively inhibits COX-1, whereas high-dose aspirin and other traditional NSAIDs inhibit both COX-1 and COX-2. The same review notes that inhibiting COX-2 through acetylation of serine-516 requires higher doses given repeatedly (650 mg, 4–6 times daily), because nucleated cells resynthesize the enzyme (PubMed).
  4. Aspirin-triggered eicosanoids. In a 1995 study of human endothelial cells incubated with neutrophils, aspirin triggered the formation of a previously unrecognized class of eicosanoids, 15R-epimers of lipoxins, formed through interaction of acetylated COX-2 and 5-lipoxygenase; neutrophils exposed to 15R-HETE also produced them. One of them, 15-epi-lipoxin A4, inhibited leukotriene B4-mediated neutrophil adhesion to endothelial cells in the nanomolar range, and the authors suggested these compounds may contribute to aspirin's therapeutic effects. This was a cell study (PubMed).
  5. Salicylate metabolites. Nonspecific esterases in the liver and, to a lesser extent, the stomach hydrolyze aspirin to salicylic acid, so that only 68% of an oral dose reaches the systemic circulation as aspirin. Aspirin's serum half-life is about 20 minutes; the half-life of salicylic acid depends on dose, because its conversion to salicyluric acid and salicyl phenolic glucuronide saturates at low concentrations (PubMed).

Dose Ranges in Trials and Guidelines

Key Research Papers

  1. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biology 1971;231(25):232–235. — doi:10.1038/newbio231232a0
  2. 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 1988;2(8607):349–360. — PubMed PMID: 2899772
  3. 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;321(3):129–135. nejm.org/doi/10.1056/NEJM198907203210301
  4. Antithrombotic Trialists' Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373(9678):1849–1860. — doi:10.1016/S0140-6736(09)60503-1
  5. McNeil JJ, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly (ASPREE). N Engl J Med 2018;379(16):1509–1518. nejm.org/doi/10.1056/NEJMoa1805819
  6. U.S. Preventive Services Task Force. Aspirin Use to Prevent Cardiovascular Disease: Recommendation Statement. JAMA 2022;327(16):1577–1584. jamanetwork.com/journals/jama/fullarticle/2791399
  7. Rothwell PM, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010;376(9754):1741–1750. — doi:10.1016/S0140-6736(10)61543-7
  8. Burn J, et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study. Lancet 2020;395(10240):1855–1863. — doi:10.1016/S0140-6736(20)30366-4
  9. Jeffreys D. Aspirin: The Remarkable Story of a Wonder Drug. Bloomsbury, 2004 — a popular history of aspirin.
  10. 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(7329):71–86. — PubMed PMID: 11786451
  11. Jones WS, Mulder H, Wruck LM, et al. Comparative effectiveness of aspirin dosing in cardiovascular disease (ADAPTABLE). N Engl J Med 2021;384(21):1981–1990. — PubMed PMID: 33999548
  12. Maqsood MH, Levine GN, Kleiman ND, Hasdai D, Uretsky BF, Birnbaum Y. Do we still need aspirin in coronary artery disease? J Clin Med 2023;12(24):7534. — PubMed PMID: 38137601
  13. Patrono C, Burn J, Patrignani P, Langley RE. Platelet activation, aspirin, and cancer: from basic science to clinical trials. Pharmacol Rev 2026;78(1):100109. — PubMed PMID: 41592353
  14. Tacconelli S, Contursi A, Falcone L, et al. Characterization of cyclooxygenase-2 acetylation and prostanoid inhibition by aspirin in cellular systems. Biochem Pharmacol 2020;178:114094. — PubMed PMID: 32535107
  15. Clària J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci U S A 1995;92(21):9475–9479. — PubMed PMID: 7568157
  16. Needs CJ, Brooks PM. Clinical pharmacokinetics of the salicylates. Clin Pharmacokinet 1985;10(2):164–177. — PubMed PMID: 3888490
  17. Zheng X, Yue P, Liu L, et al. Efficacy between low and high dose aspirin for the initial treatment of Kawasaki disease: current evidence based on a meta-analysis. PLoS One 2019;14(5):e0217274. — PubMed PMID: 31117119
  18. Sneader W. The discovery of aspirin: a reappraisal. BMJ 2000;321(7276):1591–1594. — PubMed PMID: 11124191
  19. Desborough MJR, Keeling DM. The aspirin story — from willow to wonder drug. Br J Haematol 2017;177(5):674–683. — PubMed PMID: 28106908
  20. Stone E. An account of the success of the bark of the willow in the cure of agues. Philosophical Transactions of the Royal Society of London 1763;53:195–200. — doi:10.1098/rstl.1763.0033

PubMed Topic Searches

  1. Clinical trials on aspirin — PubMed search
  2. Systematic reviews of aspirin — PubMed search
  3. Meta-analyses on aspirin — PubMed search
  4. Treatment research on aspirin — PubMed search
  5. Mechanism studies of aspirin — PubMed search
  6. Epidemiology of aspirin — PubMed search

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