Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Further digestive dangers of antithrombotic agents
- Michael I Carter (10 October 2006)
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Glycoprotein IIb/IIIa antagonist-induced thrombocytopaenia increases bleeding and death - are statins the answer?
- Amit Patel (10 October 2006)
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Combination Antiplatelet Therapy-Are we following the guidelines?
- Surya P Rajeev, Satheesh B Nair,Clinical Fellow in Cardiology,Manchester Heart Centre (12 October 2006)
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Recommended strategy to prevent upper gastrointestinal bleeding from antiplatelet agents
- Grant E Sklar (17 October 2006)
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Michael I Carter, Consultant Anaesthetist Luton & Dunstable Hospital NHS Trust, Lewsey Road. Luton Beds. LU4 0DZ
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Professor Sung states that the recommended strategy to prevent upper gastrointestinal bleeding in patients on one or two antiplatelet agents is open to debate, though the use of Proton Pump Inhibitors is recommended.There is NICE guidance on the use of PPIs in this situation.(1) I have performed five groups of audits of fifty deceased patient records in the last three years, using some of the "trigger tools" of the Institute for Healthcare Improvement. This includes identifying those who have had Clostridium difficile infection. In the last audit where the average age at death was just over 80 years of age, 20 of the patients were on PPIs, 16 patients were on aspirin alone, one on asasantin, and 3 were on aspirin with clopidogrel. Five patients had C.diff in the days before they died, and 2 others had had C.diff on previous admissions. Four of the patients with current C.diff were also taking PPIs during their last admission. A study is needed to monitor C.diff occurence in the group on aspirin alone, and those on clopidogrel, aspirin and a PPI. PPIs will lessen the hydrogen ion concentration in the stomach about 1000-fold throughout the 24 hour period. PPIs are thought to increase C.diff occurence 2-3 fold.(2, 3) H2 blockers are not thought to increase C.diff to this significant extent. 1. National Institute for Clinical Excellence. Technology Appraisal Guidance- No.7. Guidance on the use of Proton Pump Inhibitors in the Treatment of Dyspepsia, July 2000. 2. Proton Pump Inhibitors as a risk factor for Clostridium difficile diarrhoea. R. Cunningham, B. Dale, B. Undy, N. Gaunt. Journal of Hospital Infection (2003) 54, 243-245. 3. Risk of Clostridium difficile diarrhoea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. S. Dial, K. Alrasadi, C. Manoukian, A Huang, R. Menzies. Canadian Medical Association Journal. July 6, 2004; 171, 33-38. Competing interests: None declared |
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Amit Patel, Senior House Officer in Cardiology The Heart Hospital, University College London Hospital NHS Foundation Trust, London, W1G 8PH, UK
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Sung[1] comments on the bleeding risks associated with anti-platelets agents, either alone or in combination, and possible strategies for risk reduction. Although glycoprotein (GP) IIb/IIIa antagonists were not discussed, their use in cardiology patients, in combination with aspirin, clopidogrel and heparin, has increased markedly in the acute setting, particularly in those receiving percutaneous coronary intervention (PCI). Adjusted registry data suggests that they increase the risk of bleeding at least twofold in these patients, particularly when combined with heparin.[2] Both heparin and GP IIb/IIIa antagonists can cause thrombocytopaenia and increase the risk of mucosal, gastrointestinal and intracranial bleeding. The reported incidence of GP IIb/IIIa antagonist-induced thrombocytopaenia varies depending on the agent and platelet definition used. However, its presence is associated with an increase in severe bleeding, a higher risk of recurrent myocardial infarction, a greater transfusion requirement, and an increased 30-day[3] and one-year risk of death.[4] There are some data that suggest statins may reduce the risk of gastrointestinal bleeding in all groups of patients presenting as an acute coronary syndrome (ACS), including those taking GP IIb/IIIa antagonists.[5] It is thought they increase the systemic production of protective prostaglandins that may protect the gastric mucosa and prevent gastrointestinal bleeding.[5] [1] Sung JJY. Combining aspirin with antithrombotic agents. BMJ 2006;333:712-713. [2] Horwitz PA, Berlin JA, Sauer WH, Laskey WK, Krone RJ, Kimmel SE. Bleeding risk of platelet glycoprotein IIb/IIIa receptor antagonists in broad-based practice (results from the Society for Cardiac Angiography and Interventions Registry). Am J Cardiol 2003;91:803-6. [3] Merlini PA, Rossi M, Menozzi A, Buratti S, Brennan DM, Moliterno DJ, Topol EJ, Ardissino D. Thrombocytopenia caused by abciximab or tirofiban and its association with clinical outcome in patients undergoing coronary stenting. Circulation 2004;109:2203-6. [4] Scirica BM, Cannon CP, Cooper R, Aster RH, Brassard J, McCabe CH, Charlesworth A, Skene AM, Braunwald E. Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial. J Thromb Thrombolysis 2006;22:95-102. [5] Atar S, Cannon CP, Murphy SA, Rosanio S, Uretsky BF, Birnbaum Y. Statins are associated with lower risk of gastrointestinal bleeding in patients with unstable coronary syndromes: analysis of the Orbofiban in Patients with Unstable coronary Syndromes-Thrombolysis In Myocardial Infarction 16 (OPUS-TIMI 16) trial. Am Heart J 2006;151:976.e1-6. Competing interests: None declared |
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Surya P Rajeev, SHO,Diabetes and Endocrinolohy Prince Charles Hospital,Merthyr Tydfil,CF47 9DT, Satheesh B Nair,Clinical Fellow in Cardiology,Manchester Heart Centre
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Professor Sung has rightly pointed out the risk of gastrointestinal bleed and the need to balance between cerebrovascular or cardiovascular protection versus risk of GI bleed(1).An important factor contributing to this is the duration of therapy.The NICE assessment report on the clinical and cost effectiveness of clopidogrel in combination with aspirin versus aspirin alone in the treatment of NonSTelevation Acute Coronary Syndromes clearly sates that substantial part of the benefit derived from clopidogrel is achieved by three months,with a further small benefit over the remaining nine months(2).This is demonstrated by the CURE study as well(3).In real clinical practice,elderly patients who are on aspirin and clopidogrel combination for years and who are on triple therapy with aspirin,clopidogrel and warfarin presenting with a drop in haemoglobin values are not so uncommon.This made me do an audit of 50 patients who had a NonSTelevation ACS in the past,12 of them were on aspirin and clopidogrel for more than 12 months. The cost effectiveness should also be taken into consideration.Even though treatment with clopidogrel for twelve months remained cost effective,provisional findings indicate that shorter traetment duartions of three months may be cost effective in low risk patients(2). References 1.Combining Aspirin with Antithrombotic Agents,BMJ2006;333:712-713 2.NICE assessment report:A rapid and systematic review of the clinical and cost effectiveness of clopidogrel used in combination with aspirin compared to aspirin alone in the treatment of Non Stelevation ACS;23 March 2004 3.The Clopidogrel in Unstable Angina to prevent Recurrent Events,New England Journal of Medicine2001;345:494-502. Competing interests: None declared |
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Grant E Sklar, Senior Lecturer Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543
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I read with interest the recent editorial by Professor Sung in the October 7 issue of the Journal. (1) Although he clearly stated that most of the recommendations in the Table were not evidence-based, I have several concerns about the recommendations given. Firstly, now that this has been published in the Journal, I am afraid people will "forget" that most of the recommendations are not evidence-based when they implement them in practice (a type of so-called "reader bias" (2)). This will lead to these recommendations becoming THE standard of practice, and this may actually hinder the conduct of further studies. Secondly, the author states that age over 65 years is a risk factor for upper gastrointestinal bleeding (UGIB) from low-dose aspirin. This is actually a controversial issue. Several studies have concluded that age is not an independent risk factor for UGIB with low-dose aspirin. (3-6) Lastly, there are no references to support the classification of low risk, moderate risk and high risk based on the number of risk factors present. As a specific example, is the author suggesting that all patients with moderate risk about to be started on low-dose aspirin alone be empirically treated with an H. pylori eradication regimen before starting aspirin? I am unaware of any studies to support such a suggestion. The studies that have assessed H. pylori eradication in low-dose aspirin users have been for secondary prevention (i.e., to prevent a recurrent bleed or ulcer), not for primary prevention. (7,8) If we are to routinely test all moderate and high risk patients for H. pylori before starting aspirin (either non-invasive tests or endoscopic tests), the costs would be prohibitive. I would strongly agree with Professor Sung that more studies are needed in this area - both clinical trials and cost-effectiveness analyses - before his recommendations are routinely implemented. References 1. Sung JJY. Combining aspirin with antithrombotic agents. BMJ 2006;333:712-3. 2. Owen R. Reader bias. JAMA 1982;247:2533-4. 3. Ng W, Wong WM, Chen WH, et al. Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease. World J Gastroenterol 2006;12:2923-7. 4. Serrano P, Lanas A, Arroyo MT, Ferreira IJ. Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases. Aliment Pharmacol Ther 2002;16:1945 -53. 5. Lanas A, Fuentes J, Benito R, et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002;16:779-86. 6. Lanas A, Bajador, Serrano P, et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal anti-inflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343:834-9. 7. Chan FKL, Chung SCS, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001;344:967-73. 8. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrence of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002;346:2033-8. Competing interests: None declared |
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