BMJ  2005;330:1440-1441 (18 June), doi:10.1136/bmj.330.7505.1440

Education and debate

For and against

Aspirin for everyone older than 50?

FOR

¹ Welsh Aspirin Group, Department of Epidemiology, Statistics and Public Health, Cardiff University, Llandough Hospital, Penarth CF64 2XW

Current population screening for vascular disease is neither efficient nor effective. Peter Elwood and colleagues believe we should have a public information strategy highlighting the benefits (and risks) of aspirin for older people, but Colin Baigent argues that the evidence of benefit is not yet strong enough

Introduction

It is 30 years since the first randomised trial was published showing a link between aspirin and myocardial infarction.¹ We believe that the evidence now supports more widespread use of aspirin prophylaxis, and there needs to be a strategy to inform the public and enable older people to make their own decision. The evidence focuses on a crucial question—namely, at what age does the balance between benefit and risk justify low dose aspirin prophylaxis? Of further relevance is a possible reduction of cancer and dementia by aspirin.

Recommendations for aspirin prophylaxis

Although several groups have recommended aspirin prophylaxis based on age alone, including a recommendation of daily aspirin for everyone over 50,^{2 3} cardioprotection is usually given only to people at vascular risk. Many formulas are available to assess risk, and one of these⁴ is the basis of the recommendation that prophylactic aspirin be considered if the five year risk of a vascular event is 3% or more.⁵

Application of the Framingham risk formula⁴ to the Caerphilly cohort,⁶ a representative population sample of men aged 45-59 years, shows that half the men had a risk above 3% by the age of 45. This is apparent both from the application of risk assessment formulas (table 1) and from the actual occurrence of vascular events (table 2). Comparable data for women are available from the Heart Beat Wales survey,⁷ and estimates based on these show a 3% five year risk is reached by half the women by age 50 (table 1).

View this table: [in this window] [in a new window]   Table 1 Estimates of age at which 50% and 80% of population reach a 3% risk of a vascular event within the next five years and 1% risk in one year

 

View this table: [in this window] [in a new window]   Table 2 Risk of a vascular event in Caerphilly cohort based on numbers of events observed and numbers predicted with Framingham risk formula5

 

Risk of undesirable effects

Aspirin is inappropriate for people with known contraindications. At low dose, however, undesirable effects are unusual and seldom serious,⁸ and probably 90-95% of the population could take low dose aspirin without problems. The advice that people without symptoms should consult a doctor before starting aspirin prophylaxis is unreasonable and places the doctor in an impossible position. Without symptoms or a history suggestive of a contraindication, undesirable effects cannot be predicted. Each person, not a doctor, should evaluate the risks and benefits. A heart attack or stroke has serious physical and psychological effects as well as effects on the family, work colleagues, and friends. Most older people know this from experience and many will dread a vascular event. They are likely to accept a small increased risk of bleed or other side effect in exchange for a reduced risk of a heart attack or stroke.

Other benefits

Evidence is growing that regular aspirin may reduce cancer and dementia as well as vascular events. A low incidence of cancer has been reported in habitual aspirin users.⁹ In addition, studies have shown apoptosis in cancer cells cultured with salicylate,¹⁰ a reduction in cancer in people with a genetic mutation that mimics an aspirin effect,¹¹ and secretion of salicylate by plants to achieve programmed cell death.¹² Randomised controlled trials have detected a reduction in the growth of colon adenomas with aspirin,¹³ but no adequate randomised controlled trial of cancer prophylaxis by aspirin has been reported.

By reducing the incidence of cerebrovascular events, aspirin is already of value in reducing dementia. Evidence also suggests that aspirin and other non-steroidal anti-inflammatory drugs could reduce Alzheimer's disease.¹⁴

These further benefits of aspirin are not proved in randomised trials. However, if they occur they would be a bonus to the vascular protective effects and could affect some people's decision whether to take aspirin.

Why we need treatment for everyone

Within the United Kingdom, population screening to identify and treat those at high risk does not seem to be successful in controlling vascular disease. Many people at high risk remain undetected, and a survey of 1300 patients known to be at high risk within a representative sample of practices across Wales in 2003 found that only about half (53%) were taking aspirin.

Health promotion initiatives seem to achieve little behavioural change in the general community,¹⁵ and without additional social support, health education seems effective only in higher social classes. Although not an alternative to health promotion, nor a substitute for the appropriate treatment of high blood pressure, raised blood lipids concentrations, etc, the possibility that a simple, daily, inexpensive low dose pill would achieve a reduction in vascular disease events, and might achieve reductions in cancer and dementia, without the need for screening, deserves serious consideration.

Although we judge that aspirin should be taken from around 50 years, we recommend wide discussions on the threshold that include the general public, and we insist that the general public should be well informed and the final decision should lie with each person. Such discussions would not only fulfil the recommendations in the recent white paper that "people should make their own choices... but these choices should be informed by good information and advice about the choices available... to help people make and carry out the right decisions for their own health."¹⁶ They would also help meet expectations expressed by members of the public questioned in a recent King's Fund survey.¹⁷ Eighty six per cent of respondents said that information should be provided to the general public, and half said that the NHS should provide information, advice and support "To enable everyone to prevent illness and lead healthier lives." In fact, what we recommend would help put the public back into public health.—Peter Elwood, Gareth Morgan, Ginevra Brown, Janet Pickering

---

Contributors and sources: PE directed the Caerphilly Cohort Study, has been responsible for studies of aspirin in Wales, led the research leading to this article, and is lead author and guarantor. GM took part in discussions during the research leading to this article and helped write it. GB did some of the statistical analyses that guided the thinking behind this article. JP was involved in the studies on aspirin, worked with GB on the statistical analyses, and had a minor part in writing the article.

Competing interests: None declared.

References

1. Elwood PC, Cochrane AL, Burr ML, Sweetnam PM, Williams G, Welsby E, et al. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. BMJ 1974;i: 436-40.
2. British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, British Diabetic Association. Joint British recommendations on prevention of coronary heart disease in clinical practice: summary. BMJ 2000:320; 705-8.[Free Full Text]
3. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003;326: 1419-24.[Abstract/Free Full Text]
4. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J 1991;121: 293-8.[CrossRef][ISI][Medline]
5. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002;136: 161-72.[Abstract/Free Full Text]
6. Caerphilly and Speedwell Collaborative Group. Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Community Health 1984;38: 259-62.[Abstract]
7. Health Promotion Authority for Wales. Heart of Wales: clinical results of the Welsh heart health survey. Cardiff: Welsh Heart Programme Directorate, 1985. (Heartbeat Wales report 20.)
8. Gandhi TK, Weingart SN, Borus J, Seger AC, Peterson J, Burdick E, et al. Adverse drug events in ambulatory care. N Engl J Med 2003;348: 1556-64.[Abstract/Free Full Text]
9. Baron JA. Epidemiology of non-steroidal anti-inflammatory drugs and cancer. Prog Exp Tumor Res 2003;37: 1-24.[ISI][Medline]
10. Din FVN, Dunlop MG, Stark LA. Evidence for colorectal cancer cell specificity of aspirin effects on NFB signalling and apoptosis. Br J Cancer 2004;91: 381-8.[ISI][Medline]
11. Davey Smith G, Ebrahim S. Mendelian randomisation: prospects, potential and limitations. Int J Epidemiology 2004;33: 30-42.[Free Full Text]
12. Mur LAJ, Brown IR, Darby RM, Bestwick CS, Bi YM, Mansfield JW, et al. A loss of resistance to avirulent bacterial pathogens in tobacco is associated with the attenuation of a salicylic acid-potentiated oxidative burst. Plant J 2000;23: 609-21.[CrossRef][ISI][Medline]
13. Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, et al. A randomised trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348: 891-9.[Abstract/Free Full Text]
14. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Brietner JC, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology 2004;23: 159-69.[CrossRef][ISI][Medline]
15. Ebrahim S, Davey Smith G. Systematic review of randomised controlled trials of multiple risk factor interventions for preventing coronary heart disease. BMJ 1997;314: 1666-74.[Abstract/Free Full Text]
16. Department of Health. Choosing health: making healthier choices easier. London: Stationery Office, 2004.
17. King's Fund. Public attitudes to public health policy. London: King's Fund, 2004.

(Accepted 22 March 2005)

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