Salicylic acid is a benzene ring with a phenol (HO) group and a carboxylic acid (COOH) group. Whereas other scientists had focused on the carboxylic acid group, Dr Felix Hoffman, a German chemist at Friedrich Bayer and Co, concentrated on the phenol group and managed on August 10^th 1897 to acetylate the phenol group and produce pure stable acetylsalicylic acid (ASA) for the first time^1,2. In this work he was supported and inspired by a number of other scientists including Arthur Eichengrün, Carl Duisberg and Wilhelm Siebel^1,2,4. Dr Hoffman’s discovery was the first time a drug had been made synthetically and was the birth of both aspirin and the pharmaceutical industry ². After recognising the importance of Hoffman’s discovery Professor Heinrich Dreser, Head of the Pharmacology Institute at Bayer, tested it first on himself, then in a series of animal experiments before successful clinical trials in humans¹.

The new compound was named and registered Aspirin on February 1^st1899. The ‘A’ comes from acetyl and ‘spir’ from the first part of Spirea ulmaria (Meadowsweet) a botanical source of salicylic acid¹.

Aspirin in cardiovascular disease prevention

In the 1950s Laurence Craven, a general practitioner from California, published his work using aspirin to prevent vascular events. Craven recommended aspirin for patients 45-65 years of age who were at risk of a heart attack due to weight or sedentary lifestyle. He found that in those who took aspirin no myocardial infarctions (MIs) occurred. Craven also observed that none of his patients taking aspirin experienced a stroke⁶.

Many different scientists contributed to our understanding of how aspirin effects platelet function. Dr Harvey Weiss in the late 1960s reported that aspirin displayed a rapid and irreversible inhibition of platelet aggregation⁷. It was Sir John Vane’s research group who were first to discover the role of prostaglandins in haemostasis ⁴. In 1971, Vane described aspirin’s inhibition of prostaglandin synthesis in a Nature publication⁸. In 1982 he was awarded the Nobel Prize for Medicine in recognition of this work and aspirin started to become established as a drug for treating and preventing cardiovascular. In 1985 Carlo Patrono with his research group showed that low dose aspirin permanently inhibits thromboxane⁹.

In 1974 realising the growing potential for aspirin and the importance of uniting the research community to study its benefits Nick Henderson FIPR HonFRCVS, established the International Aspirin Foundation to increase the knowledge and understanding of the drug. He remained an active member up until his death, age 92 in December 2018.

Professor Richard Peto, an epidemiologist at Oxford University, published in 1980 a meta-analysis of 6 trials and showed a highly significant 23% reduction in vascular disease mortality for those taking aspirin¹⁰. Interestingly this work also inspired Archie Cochrane to set up the Cochrane collaboration with the aim of organising medical research findings and facilitating evidence-based choices for clinicians, patients and policy makers².

In 1988 the Second International Study of Infarct Survival ISIS-2¹¹ showed the benefits of aspirin after a heart attack. As a result, cardiologists start using aspirin as immediate standard practice for suspected MI. ISIS-2 also showed the importance of large randomised trials with thousands of patients in order to demonstrate these lifesaving benefits.

Also, in 1988 Physicians Health Study provided evidence that long term low dose aspirin resulted in a reduction in MI and a role for aspirin in the primary prevention ischemic heart disease¹².

In 1994 The Antiplatelets Trialist Collaboration confirmed that aspirin could prevent further cardiovascular events and death in people with established vascular disease¹³. Then, in 2002, The Antithrombotic Trialist’ Collaboration¹⁴ publish a meta-analysis demonstrating the antiplatelet effect of aspirin and its role in preventing death, myocardial infarction and stroke in high risk patients. Aspirin also has an important role in the immediate treatment of minor stroke in order to prevent recurrent stroke^15,16. Reviewing both its preventative effect for the two big killers cardiovascular disease and cancer the US Preventative Task Force¹⁷ in 2009 recommend aspirin for primary disease prevention in certain groups.

A 2020 publication looking at the secondary prevention of cardiovascular disease has shown that aspirin is still one of the best options¹⁸.

Aspirin in cancer prevention and management

1988 Professor Gabriel Kune noticed that people taking aspirin had a 40% lower risk of developing cancer of the large intestine¹⁹. Other research has further supported this finding and a time dependent reduced incidence in colorectal cancer has been observed^20-22. In 2011, Sir John Burns²³ showed the role of aspirin in helping to prevent cancer in carriers of hereditary colorectal cancer.

Further studies are ongoing to fully understand aspirins role in cancer prevention including the role of aspirin in reducing the risk of metastatic spread^24,25 in established cancer.

Primary disease prevention

Results from recent primary prevention trials such as ASCEND, ASPREE, ARRIVE, AspECT seAFOod etc. have triggered a lot of debate and discussion²⁶ and prompted refinement of further research studies. It is becoming apparent that an individualised approach is important as well as careful consideration of age and all risk factors. Individualised dosing regimens will be needed to fully exploit the potentially lifesaving benefits of this fascinating drug. A one size fits all approach is not appropriate and factors such as increased platelet turnover in certain disease conditions e.g. diabetes leads to ‘unblocked’ platelets in the circulation when a once daily aspirin regime is used⁴, in addition body weight can effects aspirin effectiveness ²⁷.