Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Thank god I'm allergic to Aspirin.......
- Phillip J. Colquitt (19 June 2005)
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Don't Forget Aspirin Resistance
- Ketan K Dhatariya (20 June 2005)
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What about total mortality?
- Jan P Vandenbroucke (20 June 2005)
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Passing the buck?
- Arunachalam Kumar (21 June 2005)
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Garlic may be the answer.
- Norman K Gibbon (21 June 2005)
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Everything Hazy
- Naveed S Aziez (22 June 2005)
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Avoid the harm
- Lexley M Pinto Pereira (22 June 2005)
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Re: Garlic may be the answer.
- Christopher Anton (22 June 2005)
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Total mortality and hypersensitivity to salicylate?
- Ellen C G Grant (22 June 2005)
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The strange case of the missing premise
- James Penston (23 June 2005)
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Re: Total mortality and hypersensitivity to salicylate?
- Stevie M Gamble (23 June 2005)
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Sins of commission and omission
- Dougal J Jeffries (27 June 2005)
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Phillip J. Colquitt, Independent Independent Comment
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.....and even if I wasn't, I'm sceptical about everyone doing anything. Especially so as applies the “chemicalization” of eating - eg. ordinary people going about talking about "protein" as if they know what that means. And "my cholesterol", as if that is meaningful. I prefer words like "meat" and "carrots". And “fat” is so much better a word than “obese”. And “lazy sod” is so much more descriptive than “not motivated”. Competing interests: Over 50. |
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Ketan K Dhatariya, Consultant Endocrinologist Norfolk and Norwich University Hospital NHS Trust
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It is surprising that neither author involved in the debate for and against the prescribing of aspirin for those over 50 mentions the growing notion of aspirin resistance. This term is used to describe not only an absence of the expected pharmacologic effects of aspirin on platelets, but also poorer than expected clinical outcomes. Thus there are two definitions of this condition - biochemical aspirin resistance, in which the in vitro activation of platelets is persistent or clinical aspirin resistance where there are recurrent vascular events in individuals already on aspirin. Several authors have now documented that a substantial minority of individuals may have either total or partial aspirin resistance. These studies have been summarised elsewhere (1). Whilst these studies may have methodological differences, they suggest that between 5% and 55% of treated individuals may have some degree of aspirin resistance. Recent data suggests that even in individuals who are at potentially greater risk of cardiovascular events than a normal population, a substantial proportion have insulin resistance (2). An increased level of complexity with this argument is that it has yet to been shown whether aspirin related side effects are less common in aspirin resistant individuals. If they are not, then universal aspirin administration may be associated with an increase in side effects with no concurrent decrease in cardiovascular events. Until these issues have been further investigated, it seems unwise to recommend aspirin for everyone over 50 years old. (1) Sanderson S, Emery J, Baglin T, Kinmouth A. Aspirin resistance and its clinical implications. Ann.Intern.Med. 2005;142:370-80. (2) Fateh-Moghadam S, Plöckinger U, Htun P, Reuter T, Ersel S, Gawaz M et al. Prevalence of aspirin resistance in patients with type 2 diabetes. Acta Diabetol. 2005;42:99-103. Competing interests: None declared |
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Jan P Vandenbroucke, Professor of Clinical Epidemiology 2300RC Leiden, The Netherlands
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It is interesting that neither side of the debate looks at total mortality in trials that came close to enrolling the general population (i.e., low risk trials), for which the answer is already patently clear: zero effect (1,2). By the way, the same applies to statins (3). 1. http://www.jr2.ox.ac.uk/bandolier/band105/b105-5.html 2. http://www.acponline.org/journals/news/mar02/aspirin.htm 3. http://www.ti.ubc.ca/pages/letter48.htm Competing interests: None declared |
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Arunachalam Kumar, Professor of Anatomy Kasturba Medical College, Mangalore, 575001, India
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I am quite surprised that the authors have wily nily let the profession off the hook vis-a-vis the risks of aspirin prophylaxis for myocardial infarction. To leave the onus of decision taking on the patient, instead of being an informed mentor in the fight against vascular disease, is in my view, alarming. How can (I quote from the article),'each person, not a doctor, should evaluate the risks and benefits' be of much value to decison making in a patient unaware of drugs and pharmacotherapeutics? In the same article later,the authors advice that,'they (the patients) 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' is if anything,an indirectly offered 'medical advice' from doctors. Passing the buck is impossible when the buck stops here, in the consultating room Competing interests: None declared |
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Norman K Gibbon, Consultant urologist, Rtd. 30, Barton Heys Rd.,Formby, Liverpool, L37 2EY.Garlic may be the answer.
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Instead of worrying over the side- effects of aspirin,why do we not promote garlic which has similar anti-platelet properties and many more vascular advantages as well without the risk of adverse reactions?(There is plenty of evidence for this in the literature which includes double- blind clinical trials using aged garlic which is odourless). Eight years ago, I had a quadruple coronary bypass operation. I refused to take aspirin post-operatively as I have a bad history of peptic ulcer. Clopidogral resulted in several haemoptyses and,having researched the literature (very carefully!) I opted for Kyolic Aged Garlic, mg 600 b.d. Now aged 86,I have had no reason to regret this decision. Competing interests: None declared |
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Naveed S Aziez, ER Supervisor Aga Khan University Hospital
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I am surprised that this article, which only elaborates what is already known,finds a place in BMJ. This should have been more expressive some more research should have gone into it.References to data and research over the last 30 years alongwith the benefits or otherwise over the years should have been added to it.What it adds as benefits (reduced risk of cancer and dementia)are also not proven. This could have been published 30 years ago and nobody would have been able to tell the difference. Competing interests: None declared |
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Lexley M Pinto Pereira, Senior Lecturer Faculty of Medical Sciences, The University of the West Indies, St Augustine, Trinidad, West Indies
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Recommending aspirin for everyone over 50 has overlooked a dose that looks at the ratio of benefit to risk, considering an individual still has at least a third of life span remaining, and older hypertensives are susceptible to haemorrhagic stroke. The debate of how low is low has gone on long enough with no definite answer beyond 75mg to over 4 times its multiple at 325mg for secondary prevention of cardio and cerebrovascular thrombotic disease. Aspirin across the board for primary prevention may be considered in patients with a 10% risk of coronary heart disease and demands looking at the risk-benefit balance between the number of myocardial infarctions that can be prevented versus the risk of hemorrhagic stroke and gastro- intestinal bleeds. Bandolier has looked at randomnised controlled trials in patients at low risk of CVD and failed to find sufficient evidence of benefit (1). A metanalysis of subjects at moderate risk indicates the risk of thrombotic stroke is overemphasised and overpowers the risk of major bleeds even from low dose aspirin (2). Cost is often a limiting factor in Trinidad and Tobago where enteric- coated or slow release preparations are not available in the public sector and not many patients can afford these preparations which may reduce the incidence of gastrointestinal blood loss. Patients must take responsibility for their health, but if they are also expected to make their choice of therapy, why need a physician at all? The evidence of benefit of using aspirin as primary prevention to influence cardiovascular outcomes is still awaited and till it is generated: avoid the possible harm. 1.http://www.jr2.ox.ac.uk/bandolier/band105/b105-5.html 2.Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324: 71- 86 Competing interests: None declared |
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Christopher Anton, Administrative Co-ordinator West Midlands Centre for ADR Reporting B18 7QH
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Dear Editor Garlic may indeed be the answer [1] but we shouldn't fall into the trap of thinking that it is entirely free from adverse effects because it is a natural product. The MHRA (as of January last year) had received 5 adverse reaction reports of 11 reactions to Allium sativum. [2] Worryingly 3 of these concerned suspected drug interactions. Many reports of adverse reactions to garlic will also go unreported. References 1. Gibbon NK. Garlic may be the answer. Available at http://bmj.bmjjournals.com/cgi/eletters?lookup=by_date&days=1#110159 (Accessed 23/6/05) 2. MHRA. Adverse drug reactions online information tracking - Drug analysis print. Available at http://www.yellowcard.gov.uk/dapdocs/allium_sativum.pdf (Accessed 23/6/05) Competing interests: None declared |
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Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU, UK
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Herbalists may recommend intake of natural foods or herbs containing saliclyate as a safer alternatives to aspirin.1 However, there is some evidence of adverse effects of foods with a high salicylate content. Feingold's hypothesis was that many hyperactive children are hypersensitive to artificial colours and flavours and other chemical additives and naturally occurring substances in foods. Feingold's additive and salicylate-free Kaiser-Permenente diet for the treatment of hyperactive children can be effective. An appropriate diet can reduce the use of drug medications.2 Studies of irritable bowel syndrome identified adverse food reactions to foods with a high salicylate or amine content when diarrhoea is predominant.3 In a study of coeliac disease symptoms were especially provoked by amine, salicylate and soy.4 Aromatic volatile ingredients in food were found to elicit pseudoallergic reactions in chronic urticaria. However, histamine, salicylate, and a direct mast-cell histamine release were not found to be involved in this type of reactivity to naturally occurring pseudoallergens.5 Reye's syndrome, a severe sepsis-like disease thought to be caused by a hypersensitivity to salicylate in children with mild viral infections, has virtually disappeared from much of the world after the use of salicylate in febrile children was successfully discouraged.6 At what age does aspirin suddenly become safe to be used? How does use in pregnancy affect the foetus? Is the child sensitised to salicylate and more likely to become hyperactive? The lack of safety of aspirin use in adults may be why there is no overall mortality benefit in population trials. 1 McMullen MK. Are we medicating a nutritional deficiency? http://bmj.com/cgi/eletters/330/7505/0-c#110006, 19 Jun 2005 2 Carter CM, Urbanowicz M, Hemley R, et al. Effects of few food diet in attention deficit disorder. Arch Dis Child 1993: 69:564-8. 3 Niec AM, Frankum B, Talley NJ. Are adverse food reactions linked to irritable bowel syndrome? Am J Gastroenterol. 1998; 93: 2184-90. 4 Faulkner-Hogg KB, Selby WS, Loblay RH. Dietary analysis in symptomatic patients with coeliac disease on a gluten-free diet: the role of trace amounts of gluten and non-gluten food intolerances. Scand J Gastroenterol. 1999; 34: 784-9. 5 Zuberbier T, Pfrommer C, Specht K, et al. Aromatic components of food as novel eliciting factors of pseudoallergic reactions in chronic urticaria. J Allergy Clin Immunol. 2002 Feb;109(2):343-8. 6 Clark I, Whitten R, Molyneux M, Taylor T. Salicylates, nitric oxide, malaria, and Reye's syndrome. Lancet. 2001; 357: 625-7. Competing interests: None declared |
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James Penston, Consultant Physician/Gastroenterologist Scunthorpe General Hospital, Cliff Gardens, Scunthorpe, North Lincolnshire DN15 7BH
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Editor, On the one hand, Elwood et al. state that “Each person, not a doctor, should evaluate the risks and benefits” whilst, on the other, that ”Health promotion initiatives seem to achieve little behavioural change… health education seems effective only in higher social classes.” [1] Not only are these statements inconsistent, but the notion that the majority of patients would be capable of weighing up the benefits and risks without considerable guidance is fanciful. Yet more problems arise on a closer examination of the argument used by the authors to justify the use of aspirin in everyone over the age of fifty years. This may be summarised as follows: more than half of all individuals older than 50 years have a >3% five-year risk of a cardiovascular event; adverse drug reactions due to low dose aspirin are unusual and seldom serious; aspirin may have additional benefits including reducing the risk of cancer and dementia; attempts to target high risk groups have failed; therefore, all individuals over the age of 50 years should be given aspirin. This argument is, of course, flawed. Baigent, in the opposing article, [2] provided ample reasons to dismiss the reliability of each of the first three premises. Indeed, Elwood et al. did themselves few favours by focusing on epidemiological data that were more than 20 years old, by citing an unconvincing paper in support of their claims about the side-effects of aspirin, and by raising the issues of cancer and dementia, neither of which are supported by robust data. However, even if all the premises are accepted, they could not deliver the conclusion without any reference to the benefits expected from aspirin therapy. There is, though, a ready explanation for this ‘missing premise’. If Elwood et al. had specified a risk reduction with aspirin, they would have had to relate this to the type of patients studied; but, as soon as subgroups were introduced, the evidence for the widespread use of aspirin would simply evaporate. No wonder they remained silent on this matter. To those who enthusiastically support the “polypill approach” to medicine, the case made by Elwood et al. for the use of aspirin in all patients over 50 years of age must be very disappointing. However, if this is the best that can be done, then those who reject the medicalisation of entire populations may breath a sigh of relief. [1] Elwood P, Morgan G, Brown G, Pickering J. For and against: Aspirin for everyone older than fifty? BMJ 2005;330;1440-1. [2] Baigent C. For and against: Aspirin for everyone older than fifty? BMJ 2005;330;1442-3. Competing interests: None declared |
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Stevie M Gamble, retired HMIT EC2Y 8BL
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Ellen C G Grant notes in her Rapid Response of 22 June that ‘there is some evidence of adverse effects of foods with a high salicylate content’, as suggested by Dr Ben Feingold. Perhaps I could bring personal experience to bear; I am allergic to aspirin et al, and have life-threatening allergic responses to azo dyes, coal tar dyes and benzoate preservatives. For obvious reasons I totally exclude them from my diet, and have in the past tried excluding foods naturally high in salicylates. The difficulty is that salicylate levels vary hugely in plants depending on a host of factors. The herbalist’s injunction, for example, to harvest a specific plant by the light of the full moon, say, is not mumbo jumbo; it really does make a difference. Excluding naturally occurring salicylates is a great deal harder than it looks, and no significant conclusions can be drawn from the various attempts to do so. Incidentally, a much greater source of danger is the pharmaceutical manufacturers’ insistence on dyeing their products in pretty colours, and lacing them with large amounts of preservatives. I am unable to think of any rational explanation of how they manage to persuade regulators that these can be accurately described as inactive ingredients… Stevie Gamble Competing interests: None declared |
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Dougal J Jeffries, GP St Mary's HC TR21 0NE
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I believe that there is an important difference between causing harm by commiting an act (in this case, prescribing aspirin)and by failing to do so (not prescribing). To put it another way, the person who is persuaded, or chooses, to take aspirin for the theoretical benefit of prevention of stroke or cardiac event, but who then goes on to suffer a serious haemorrhagic event is quite rightly going to blame the aspirin and the prescriber(or themselves, if they have made the decision without medical advice). If, however, they choose not to take aspirin but go on to have a thrombolic event, there is much less cause to attribute this to failure to prescribe aspirin, which after all only reduces the relative risk and does not abolish it altogether. Last year an elderly patient of mine suffered a major G-I bleed while on aspirin (she had controlled hypertension); a fortnight later, after the aspirin had been stopped, she died of a stroke. I feel much more responsible for the first event than the second. I'm not sure if this is rational, but I think most people would feel the same. Competing interests: None declared |
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