Beginning in 1956 Aneurin Hughes, a general physician in Wales, and Bob Tonks, a technician in Materia Medica in The Welsh National School of Medicine began to publish a long series of exquisite laboratory and clinical studies of platelets, salicylates, aspirin and ‘infarctoid cardiopathy’ (myocardial infarction). First, they conducted detailed studies of the ‘clumping’ of blood platelets, and they then demonstrated that platelet ‘clumps’ could block a coronary blood vessel, thus precipitating a heart attack.  

In 1966 they gave a presentation at an international conference in which they described the use of aspirin in the treatment of ‘more than 1,000 patients’. Unfortunately, Hughes was convinced that massive doses of aspirin were necessary to maintain blood platelets in a discrete state, and in 1974 they wrote their final paper, reporting further work on salicylates and fibrinogen activity.  

In 1970, Cochrane and Elwood, in the MRC Research Unit in Cardiff, with encouragement from O’Brien, followed the work of Hughes and Tonks with a double-blind, placebo-controlled randomised trial of daily 300 mg aspirin in the secondary prevention of vascular disease mortality.The trial in 1,400 patients who had recently experienced a heart attack, showed a 24% reduction in deaths during a two-year follow-up.  The British Medical Journal published a report of the trial in1974 and this stimulated 50 years of intensive work within Wales and beyond on aspirin, heart disease and later, on cancer!

Twenty-five years later this trial was included in ‘The Top Fifty’, an evaluation in the BMJ of the published literature, based upon the number of citations of papers published during the previous 45 years.

The report of the randomised trial also stimulated Nick Henderson to establish the European (later the International) Aspirin Foundation in the same year (1974).  The Foundation encouraged research through annual conferences and through Scientific Awards. Nick remained a highly active leader of the IAF until his death, aged 92, in December 2018 and Pippa Hutchison, Executive Director joined in 2013.  A wealth of data on aspirin is available on the website of the Foundation. 

By 1980 an additional five randomised trials of aspirin and vascular disease had been reported. None achieved statistical significance at an acceptable level, and many clinicians had therefore dismissed aspirin as being of no value after infarction.  Sir Richard Peto however presented a meta-analysis of the six trials at the founding meeting of the Society for Clinical Trials in Philadelphi. The result: a 23% reduction in mortality associated with aspirin (95% confidence interval 21.7 – 24.3%), was later published as an editorial in the Lancet

Salicylates, the main molecule in aspirin, is widespread within the plant world, and during the conduct of the trial in the early 1970s I (Elwood) decided to enquire into salicylates in plants. I was told that Professor Stan Pierpoint in Rothamsted Experimental Station, the oldest agricultural research station in the world, was at that time the world expert on plant salicylates.  I wrote and asked if I could visit him.

Pierpoint expressed delight that salicylates were being investigated in human subjects. However, as we said farewell, Stan looked at me intently and said: ’Peter, skip heart disease; go for cancer!’ I had to explain to him that our resources in Cardiff were limited and an adequately powered trial on cancer would require a much longer trial with far larger numbers of patients than we could cope with.  Later, in a commentary on ‘Plant Products and Mammalian Medicine’ Pierpoint wrote: 

‘The medicinal properties of salicylates would appear to be less fortuitous and simply a logical consequence of their role in plants.‘

Twenty-five years later, in 2009, opportunity arose for work in Wales on aspirin and cancer and we conducted and published a fairly extensive review of the published evidence at that time on salicylates, aspirin and cancer.  We also set up ‘The Welsh Aspirin Group’, a somewhat loose collaboration of colleagues in Wales who had published evidence of a research interest in aspirin. 

Together, we identified a series of key issues relevant to the possible use of aspirin as a treatment of cancer and during the following 15 years we examined each of these key issues, usually by conducting appropriate searches of the published literature, followed by meta-analyses of all the data from all the relevant studies… and hence this web item!

Codicil: During the 50 years since the first trial of aspirin was reported in 1974 I (Elwood) have taken 75mg aspirin every evening (evening, because the peak risk of infarction is around 5.00 am) – except for one week in 2010. 

I was away from home, my stock of low-dose aspirin tablets ran out, and for around a week I took no aspirin.  During my first day back home I experienced pain in my left calf.  The pain, tenderness and swelling increased and so I called an ambulance.  I spent a few days in hospital on heparin, and amongst other investigations a CT scan showed several tiny pulmonary infarcts! 

Now, at age 94, I never miss a daily aspirin. I have had no further vascular symptoms or event, and I can detect no evidence of cancer!  Peter C Elwood

---

Key Messages

1. Daily low-dose aspirin is safe and there appears to be no valid evidence of deaths from bleeding attributable to low-dose aspirin.
2. Taken by patients with cancer, daily low-dose aspirin is associated with an overall 20% reduction in all-cause deaths.
3. Other benefits for patients with cancer include less metastatic spread, and a reduced risk of a vascular complication, including a heart attack. On this last… do a Google search on ‘ASPOD’.
4. If low-dose aspirin is taken it should not be stopped suddenly.