Aspirin – for whom, how much and how often
Aspirin is a remarkable drug in giving a degree of protection against the two most common disabling and life-threatening conditions – cancer and vascular disease.
It is readily available and inexpensive, effective in very small doses and protection is given by a single dose each day.
It has been recommended that around the age of about 50 years, both men and women should examine their lifestyle and consider whether or not to adopt an additional healthy behaviour. [see the section on healthy living] Around the age of 50 people should also carefully evaluate for themselves the possible benefits and the risks of adding a small daily tablet of aspirin as ‘a sixth healthy behaviour’ to further protect their health and minimise the risk of a cancer or a heart attack.
The dose of aspirin needed for protection is small – probably under 100mg once a day (the usual aspirin tablet for headache and pain relief is about 300mg). In the UK a ‘junior’ aspirin is probably ideal. This dose should be taken once a day. There is however suggestive evidence that benefit will be more certain in patients with diabetes if they take this dose twice a day. [See references 2 and 3 below]
For a number of reasons it would seem to be reasonable to advise that aspirin is taken at night [See Reference 4 below]. The activity of platelets, a key element in a heart attack, appears to be greatest early in the early morning and the risk of a heart attack is highest in the morning. In a huge study in the US the reduction by aspirin was found to be considerably greater on early morning heart attacks than on those which occurred later in the day [See reference 5]. Furthermore, the levels of gastric repair proteins are highest at night. [See references 6 and 7] Studies have also suggested a lower ambulatory blood pressure in persons taking aspirin, but only in those who took it at night. [See references 8 and 9]
Two trials have given suggestive evidence that a calcium supplement, taken along with aspirin, may greatly enhance the benefit of aspirin on polyp growth in the colon [See reference 9 below] In fact, this is not surprising because dietary calcium, and in particular the consumption of milk, has been shown to be associated with a reduction in heart disease, in stroke and in colon cancer [See references 11 and 12] It would therefore seem highly reasonable to recommend that prophylactic aspirin is taken at night, together with a glass of milk.
Finally, a warning about stopping aspirin! The natural response to a bleed is to stop the aspirin but this has been repeatedly shown to lead to a rebound in vascular disease incidence. In an overview of six randomised trials with over 50,000 subjects taking aspirin for coronary artery disease, the chance of a major heart attack 8-10 days after the withdrawal of aspirin, was increased more than three-fold [See reference 13 below]. A small randomised trial took the issue of aspirin withdrawal further and put patients who had bled onto a PPI. A random half of these patients were then put back onto aspirin, and the mortality in these patients was just over one percent, while patients not put back onto aspirin had a mortality of 10 percent. [See reference 14 below]. If aspirin prophylaxis is to be stopped, the drug should be withdrawn gradually.
- A randomized controlled trial of acetyl Salicylic Acid in the secondary prevention of mortality from myocardial infarction. Br Med J 1974;1:436-440
- The recovery of platelet cyclooxygenase activity explains interindividual variablility in responsiveness to low-dose aspirin in patients with and without diabetes. J Thromb Haemostasis 2012;10:1220-30.
- Primary and secondary prevenbtion of cardiovascular disease in diabetes with aspirin. Diabetes & Vasc Dis Res. 2012;9:245-55.
- Improving the gastrointestinal tolerability of aspirin in older people. Clinical Intervention in Ageing;2006;1:33-9
- Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians. Circulation 1990;82:897-902.
- Dramatic diurnal variation in the concentration of the human trefoil peptide TFF2 in gastric juice. Gut 2001;48:648-55. et al 2001;
- The diurnal rhythm of the cytoprotective trefoil protein TFF2 is reduced by factors associated with gastric morbidity; ageing, H pylori infection and sleep deprivation. Am J Gastroenterol 2005;100:1491-7.
- Ambulatory blood pressure control ; with bedtime aspirin administration in subjects with prehypertension. Amer J hypertension 2009;22:896-903.
- Time-dependent effects of low-dose aspirin on plasma reninactivity, aldesterone, cortisol and catecholamines. Hypertension 1999;34:34:1016-23
- Interaction of calcium supplementation and nonsteroidal anti-inflammatory drugs and the risk of colorectal adenomas. Canc Epidemiol Biomarkers Prev 14:2353-8, 2005.
- The consumption of milk and dairy foods and the incidence of vascular disease and diabetes: an overview of the evidence. Lipids 2010; 45: 925-30.
- World Cancer Research Fund/American Institute for Cancer Research: Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. AICR, Washington DC pp129-132, 2007.
- Systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006;27:2667-74
- Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomised trial. Ann Int Med 2010;152:1-9.