Pass the Aspirin

And so you should if you’ve got a headache – unless, of course, you prefer paracetamol. There can scarcely be anyone who hasn’t resorted to a dose of slightly modified salicylic acid (For the chemists: its hydroxyl group is converted into an ester group (R-OH → R-OCOCH3) in aspirin), given that the world gobbles up an estimated 40,000 tonnes of the stuff every year. It’s arguable, therefore, that an obscure clergyman by the name of Edward Stone has done more for human suffering than pretty well anyone, for it was he who, in 1763, made a powder from the bark of willow trees and discovered its wondrous property. The bark and leaves had actually been used for centuries – back at least to the time of Hippocrates – for reducing pain and fever, although it wasn’t until 1899 that Aspirin made its debut on the market and it was 1971 before John Vane discovered how it actually worked. He got a Nobel Prize for showing that it blocks production of things called prostaglandins that act a bit like hormones to regulate inflammation (for the chemists – again! – it irreversibly inactivates the enzyme cyclooxygenase, known as COX to its pals).

Daily pill popping

Aside from fixing the odd ache, over the years evidence has gradually accumulated that people at high risk of heart attack and those who have survived a heart attack should take a low-dose of aspirin every day. In addition to decreasing inflammation (by blocking prostaglandins) aspirin inhibits the formation of blood clots – so helping to prevent heart attack and stroke. Almost as a side-effect the studies that have lead to this being a firm recommendation have also shown that aspirin may reduce the risk of cancers, particularly of the bowel (colorectal cancer). Notably, Peter Rothwell and colleagues from Oxford showed that daily aspirin taken for 10 years reduced the risk of bowel cancer by 24% and also protected against oesophageal cancer – and a more recent analysis has broadly supported these findings. In addition they have also found that aspirin lowers the risk of cancers spreading around the body, i.e. forming distant metastases.

Why is aspirin giving us a headache – again?

First because a large amount of media coverage has been given to a report from Leiden University Medical Center, presented at The European Cancer Congress in September, that used Dutch records to see whether taking aspirin after being diagnosed with gastrointestinal cancer influenced survival. Their conclusion was that patients using aspirin after diagnosis doubled their survival chances compared with those who did not take aspirin. Needless to say, these words have been trumpeted by newspapers from The Times to the Daily Mail in the usual fashion (“Aspirin could almost double your chance of surviving cancer”). Unfortunately we can’t lay all the blame on the press: the authors of the report used the tactic of issuing a Press Release, a thoroughly reprehensible ploy for gaining attention when the work involved has not been peer reviewed. (The point here for non-scientists is that you can stand up at a meeting and say the moon’s made of blue cheese and it’s fine. Only after your work has been assessed by colleagues in the course of the normal publication process does it begin to have some credibility). So there’s a problem here, with what was an ‘observational study’, as to just what the findings mean – and the wise thing is to wait for the results of a ‘randomised controlled trial’ that is under way. 

The second source of mental strain is down to the ferociously named United States Preventive Services Task Force that has just (September 2015) come up with the recommendation that we should take aspirin to prevent bowel cancer. Why should we pay any attention? Because the ‘Force’ are appointed by the US Department of Health and they wield great influence upon medical practice – and because it’s the first time a major American medical organization has issued a broad recommendation to take aspirin to prevent a form of cancer.

In this latest oeuvre they confirm that the well-known risks attached to aspirin-eating (ulcers and stomach bleeding) are out-weighed by the protection against heart disease in those between the ages of 50 and 69 who are at high risk (e.g., have a history of heart attacks). If you feel your heart can take the strain you can find out your risk by using the National Heart, Lung, and Blood Institute’s online risk assessment tool. To get an answer you need to know your age, sex (i.e. gender, as its called these days), cholesterol levels (total and high density lipoproteins, HDLs – they’re the ‘good’ cholesterol), whether you smoke and your systolic blood pressure (that’s the X in X/Y).

This is such a critical issue it’s worth seeing what the Task Force actually said: “The USPSTF recommends low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults ages 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.”

If you’re younger than 50 or over 70 you’re on your own: the Force doesn’t recommend anything. And if you’re 60 to 69 the wording of their advice is wonderfully delicate: The decision to use low-dose aspirin to prevent CVD (cardiovascular disease) and colorectal cancer in adults ages 60 to 69 years who have a greater than 10% 10-year CVD risk should be an individual one.”

So that’s cleared that up …

Er, not quite. Various luminaries have been quick to demur. For example, Dr. Steven Nissen, the chairman of cardiology at the Cleveland Clinic has opined that the Task Force “has gotten it wrong.” In other words aspirin does more harm than good – though he might be a bit late as seemingly an astonishing 40% of Americans over the age of 50 take aspirin to prevent cardiovascular disease. I reckon that’s about 40 million people. Mmm … so that’s where the 40,000 tonnes goes (well, about one-fifth of it).

What’s the advice?

We’re more or less where we came in. I take an aspirin, or more usually a paracetamol, when I’ve got a stonking headache. Otherwise I wouldn’t take any kind of pill or supplement unless there is an overwhelming medical case for so doing. And pill-poppers out there might note the findings of Eva Saedder and her pals at Aarhus University that the single, strongest independent risk factor for drug-induced serious adverse events is the number of drugs that the patient is taking.

References

Rothwell, P. et al. (2012). Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials, Lancet DOI:1016/S0140-6736(11)61720-0

Rothwell P. et al. (2012). Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trial, Lancet DOI:1016/S0140-6736(12)60209-8

Lancet editorial on Rothwell et al. 2011.

Algra, A. and Rothwell, P. (2012). Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials, Lancet Oncology DOI:10.1016/S1470-2045(12)70112-2.

Frouws M et al. Aspirin and gastro intestinal malignancies; improved survival not only in colorectal cancer? Conference abstract. European Cancer Congress 2015

Press release: Post diagnosis aspirin improves survival in all gastrointestinal cancers. The European Cancer Congress 2015. September 23 2015

Cuzick J, Thorat MA, Bosetti C, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Annals of Oncology. Published online August 5 2014

U.S. Preventive Services Task Force Draft Recommendation Statement: Aspirin to Prevent Cardiovascular Disease and Cancer

Saedder, E.A. et al. (2015). Number of drugs most frequently found to be independent risk factors for serious adverse reactions: a systematic literature review. British Journal of Clinical Pharmacology 80, 808–817.

 

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