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Epidemiological modelling of routine use of low dose aspirin might withhold therapy in elderly patients
- Peter Matt, Hans-Reinhard Zerkowski (1 June 2005)
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Aspirin for all older people?
- Rachel T Iredale (3 June 2005)
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THE ASPIRIN DEBATE
- Joseph Yikona (3 June 2005)
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Preventive thearapy - to whom?
- Rachel Schwarzmann (14 June 2005)
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Response to Matt
- Mark R Nelson, Danny Liew, Melanie Bertram, and Theo Vos (30 June 2005)
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An interesting patient take on taking intermittent aspirin
- Rakesh Biswas (4 January 2006)
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The hidden risks of prophylactic aspirin in older patients
- Michal R. Pijak (24 January 2006)
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low dose aspirin helpful in stroke and coronary artery disease
- madhusudan reddy (20 February 2006)
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Peter Matt, Resident Division of Cardio-Thoracic Surgery, Hans-Reinhard Zerkowski
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We read with interest the article by Nelson and colleagues regarding the routine use of low dose aspirin in elderly patients. However, we have serious objections regarding the epidemiological modelling and its conclusions. We think that the results and the conclusions drawn lead to a false impression and might even withhold effective therapy to elderly patients. Nelson and colleagues describe an epidemiological model that essentially depends on clinical parameters and its incidence. However, most of them are not as clear as described in this study. For example, the incidence of the “acute coronary syndrome”, the “ischemic” and the “hemorrhagic” stroke are based on the ICD-10 encoding – it is generally known that the encoding often remains inadequately. In addition, low dose aspirin dependent major gastro-intestinal bleeding is not well defined. It might be incorrect to equate every gastro-intestinal bleeding not due to cancer, cirrhosis/portal hypertension, vascular malformation or inflammatory bowel disease with low dose aspirin. There is a lack of statements regarding the incidence of helicobacter pylori, stress, use of steroids and other antiinflammatory medications. In addition, the authors assume that the risk of major gastro-intestinal bleeding due to low dose aspirin is markedly increased in patients >70 years. This does not correspond to our daily practice. Even elderly patients under oral anticoagulation e.g. due to heart valve replacement do not show an increased rate of hemorrhage - most important is the INR-adjustment and not the increased age. Nelson and colleagues also describe a markedly increased rate of deaths associated with gastro-intestinal bleeding due to low dose aspirin. However, the invasive and non-invasive therapy of gastro-intestinal bleeding is advanced and the described mortality rate might be unrealistic (risk of death due to low dose aspirin described as more than 6 times higher than for an ischemic stroke). We think that this study leads to a false direction. It might even be harmful regarding the fact that elderly patients might be withheld an effective therapy. This is very unfortunate concerning the fact that patients steadily accept the prophylactic use of cardiovascular medications such as low dose aspirin. This therapy not only leads to an increased prognosis in the elderly but in particular to an increase in “years of healthy life” as described by the authors as “the most comprehensive measure of health effect”. Competing interests: None declared |
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Rachel T Iredale, Senior Lecturer University of Glamorgan
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I smiled when I saw the editorial by-line for this paper (.... the jury's still out). Because of course, there has never been any sort of ‘Jury’ on this topic at all. This debate over aspirin is one which has consumed the medical profession for over 30 years; yet there has been almost no public participation or consultation in this area. Although there are benefits to aspirin, it is considered inappropriate for individuals with known contraindications. Its effects in symptom-free subjects cannot be predicted. Standard advice is that subjects should consult a doctor before commencing aspirin prophylaxis. However, it could be argued that it is patients, not doctors, who should evaluate for themselves the possible outcomes and make decisions on the basis of their own evaluation of the risks and benefits. Aspirin is not an alternative to health promotion or behavioural change in relation to exercise and diet. Nor is it a substitute for the appropriate treatment of high blood pressure. The possibility of a simple low-dose pill taken daily with the potential to achieve reductions in vascular events, and even reductions in cancer incidence and dementia requires serious consideration, and needs greater public discussion and involvement in this debate. A simple solution to engage the public might be to ask them for example to consider the question “Should every person over 50 in the UK be taking aspirin on a daily basis?” Such a debate would be a good model for illustrating the perennial questions in medicine about benefits outweighing harms, the extent to which decision making about preventative health measures should be shared between patients and professionals, and how best to involve the public in discussions about taking individual responsibility for health which is a key objective in current healthcare policy. A Citizens’ Jury on aspirin would be a good first step forward. Competing interests: None declared |
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Joseph Yikona, SpR-Medicine & Geriatrics Ipswich Hospital IP4 5PD, UK
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The aspirin debate will continue until the end of time. This undefined jury will also have to understand the mathematics of aspirin benefit. It apparently reduces cardiovascular risk (relative risk) by 25%. This could be interpreted, wrongly or rightly, to mean that this is a drug that fails by 75%. In today's world can a drug that fails by a margin of 75% be given a licence. Scientifically its obviously more complex than this. For now we will continue to prescribe it advisedly on current evidence to reduce individual global cardiovascular risk. A Bob Geldof equivalent will arise to lead the public jury. Competing interests: None declared |
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Rachel Schwarzmann, Geriatric medicine Flieman hospital - geriatric rehabilitation center ,Haife israel 31021
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This article and the others show how hard we have to wark in order to find the elderly groups who have benefit from preventive treatment, and the trend to treat all the people with and sometime without risk factors is not a "real" medicine Competing interests: None declared |
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Mark R Nelson, Chair Discipline of General Practice University of Tasmania Private Bag 33 Hobart 7001, Danny Liew, Melanie Bertram, and Theo Vos
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We thank Matt for his comments. In response we would argue that the ICD-10 whatever its limitations is the international gold standard disease classification system. The problems in the estimation of major gastrointestinal bleeding (MGH) are alluded to in the limitations of the study section. Observational data supports our assertion that the risk of MGH is greater in the aged.(1) It is problematic to compare warfarin and aspirin as the latter has the additional risk for MGH of gastric irritation and erosion. The assertion that the “risk of death due to low dose aspirin described as more than 6 times higher than for an ischemic stroke” would seem to be based on the modelled net difference in deaths from ischaemic stroke and MGH reported in Table 4.(2) It is not correct to interpret these figures as a difference in risk of death from either cause. The results we present in Table 4 are influenced by: a) The population risk of disease from 4 specified causes; b) The case fatality rate for the specified causes; c) The risk of mortality from all other causes and; d) The relative risk of disease/death in those taking low-dose aspirin. The latter has the greatest impact. For example the point estimate of the relative risk for ischaemic stroke is 1.03.3 Hence the point estimate of ischaemic stroke deaths due to aspirin is small compared to the point estimate of MGH deaths even though: a) The incidence of ischaemic stroke is greater than that of MGH (Table 1)(2); b) The risk of death from ischaemic stroke is higher and continues for a longer time following an event (Tables 1 and 2).(2) There is no good evidence to support your final statement. Because of this and the uncertainty in the model we need a clinical trial in the aged to establish the balance of risk and benefit for aspirin in primary prevention of cardiovascular disease.(4) References (1) Hernandez-Diaz S, Rodriguez LA. Incidence of serious upper gastrointestinal bleeding/perforation in the general population: review of epidemiologic studies. J Clin Epidem 2002;55(2):157-63. (2) Nelson MR, Liew D, Vos T, Bertram M, McNeil JJ. Epidemiological modelling of routine use of low-dose aspirin in Australia for the primary prevention of coronary heart disease and stroke in those aged 70 years and above. BMJ, doi:10.1136/bmj.38456.676806.8F (published 20 May 2005). (3) Hart RG, Halperin JL, McBride R, Benavente O, Man-Son-Hing M, Kronmal RA. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses. Arch of Neurol 2000;57(3):326-32. (4) ASPREE Study Group, Nelson MR, Reid CM, Beilin LJ, Donnan GA, Johnston CI, Krum H, et al. Rationale for a primary prevention trial of low dose aspirin for major adverse cardiovascular events and vascular dementia in the elderly. ASPirin in Reducing Events in the Elderly (ASPREE). Drugs Aging 2003; 20(12):897-903. Competing interests: None declared |
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Rakesh Biswas, Associate Professor Vydehi Institute of Medical Sciences, Whitefield, Bangalore-560066
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A broad array of randomized trials have demonstrated the benefits of low doses of aspirin for both the primary and secondary prevention of CVD. Most trials demonstrate a 15% to 40% reduction in cardiovascular events with chronic aspirin use.
Unfortunately many of our patients don't consume based on that information. A few who don't relish it much have been innovative to the point of swallowing aspirin only during brief episodes of chest pain maybe once or twice a week. That has had generalist physicians (who weakly boast of belonging to a problem solving specialty)thinking. Is the aspirin effect related to its preventing thrombus formation during acute plaque fissuring in acute coronary or cerebral syndromes or does it have any effect on the chronic stable plaque? If the effect is only on the fissured plaque, which is a one time event does it justify consuming it daily? Would it be ethically justified to have a trial of aspirin to patients, administered only during episodes of sustained chest pain and not on a regular basis? Competing interests: None declared |
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Michal R. Pijak, Consultant in Internal Medicine, Rheumatology, Allergy and Clinical Immunology University Hospital,Limbova 5, 83305 Bratislava, Slovkaia
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In their study regarding epidemiological modelling in a hypothetical population of older patients taking prophylactic aspirin, Nelson et al. (1) rightly conclude that “....any benefits of low dose aspirin on risk of cardiovascular disease in people aged 70 are offset by adverse events.“ However, two things are important to point out . First, many older patients chronically use nonsteroidal anti- inflammatory drugs (NSAIDs) concomitantly with aspirin. This can be a problem since the formation of endogenous lipoxin analogues triggered by aspirin is sensitive to inhibition by both "coxibs" and conventional NSAIDs. (2) This interaction might explain the high rate of aspirin resistance and the differences in cardiovascular effects between individual NSAIDs and their use in combination with aspirin, as we have previously pointed out. (3) Second, there is evidence that sudden aspirin withdrawal may increase the risk of atherothrombotic events to patients with cerebrovascular (4) and coronary artery disease (5). Interestingly, similar risks are reported after the cessation of therapy with certain NSAIDs(6) suggesting that there may be some common mechanism responsible for these withdrawal-related cardiovascular and cerebrovascular events. References 1. Nelson MR, Liew D, Bertram M, Vos T. Epidemiological modelling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged > or =70. BMJ 2005;330:1306. 2. Fiorucci S, Distrutti E, Mencarelli A, Rizzo G, Lorenzo AR, Baldoni M, et al. Cooperation between aspirin-triggered lipoxin and nitric oxide (NO) mediates antiadhesive properties of 2-(Acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester (NCX-4016) (NO-aspirin) on neutrophil- endothelial cell adherence. J Pharmacol Exp Ther. 2004;309:1174-82. 3. Pijak MR, Huzicka I, Gazdik F. The risk for myocardial infarction with cyclooxygenase-2 inhibitors. Ann Intern Med 2005;143:616-7. 4. Maulaz AB, Bezerra DC, Michel P, Bogousslavsky J. Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Arch Neurol 2005;62:1217-20. 5. Ferrari E, Benhamou M, Cerboni P, Marcel B. Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis. J Am Coll Cardiol 2005;45:456-9. 6. Fischer LM, Schlienger RG, Matter CM, Jick H, Meier CR. Discontinuation of nonsteroidal anti-inflammatory drugs is associated with an increased risk of acute myocardial infarction. Arch Intern Med 2004;164:2472–6. Competing interests: None declared |
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madhusudan reddy, associate professor national institute of mentalhealth and neurosciences
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I would not agree that low dose aspirin causes very severe side effects which would prevent its use in stroke and coronary artery disease. side effects are there for every drug in medical literature. The benefits outweigh the adverse effects in this age group of 60-70 years. we had a case of stoke in a 70 year old male involving the left mca territory on ct scan with hemiplegia and speech defects. patient was not a smoker or hypertensive or diabetic. He improved within a week of heparin 10,000 units for 2 days and low dose aspirin of 75 mg alone which was only drug continued for a period of 5 years. All his deficits reverted to normal within 2 weeks and he has been healthy without any side effect of the drug so far. Another similar case where a male patient aged 60 years had a transient ischemic attack with giddiness and repeated episodes of loss of consciousness for few seconds. he had a magnetic resonance imaging and Computerised tomographic scan which showed no lesion in the brain. He was started on low dose aspirin of 75 mg daily for 3 months. since the patient had no symptoms for 3 months the neurologist stopped aspirin. patient had a severe chest pain and myocardial infarction exactly after 14 days and expired. considering these two cases along with similar numerous cases I would like to recommend low dose aspirin especially in old age where benefits outweigh the risks and risk of bleeding and side effects are very minimal with proper adequate monitoring of coagulation and other parameters. Editorial note
Competing interests: None declared |
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