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Rapid Responses: Rapid Responses published:
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Prescribing habits of warfarin
- Elliot F Epstein, Anil Kumar (23 January 2006)
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Primum non nocere (or sins of commission !)
- Andrew P Davie (24 January 2006)
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Genetic testing may help predict adverse events from warfarin
- Simon P Sanderson, Jon Emery, Julian Higgins, and Mark Kroese (25 January 2006)
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Barriers to the use of warfarin in non-valvular atrial fibrillation
- Melina Gattellari, John M. Worthington, Nicholas A. Zwar, Sandy Middleton (26 January 2006)
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Elliot F Epstein, Consultant Physician Walsall Manor Hospital, Moat Road, Walsall, WS2 9PS, Anil Kumar
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Choudhry et al report that physicians do not change their prescribing habits of warfarin if a patient with known atrial fibrillation (AF) is admitted with ischaemic stroke. It is probably fair to state that many doctors learn from their own mistakes to a greater extent compared to the mistakes of their peers. Imagine a scenario of a particular doctor learning that he or she omitted to anticoagulate a suitable patient with AF. If the doctor later learns that the patient suffered an avoidable and disabling ischaemic stroke then it is likely his or her clinical practice would change, particularly if a clinical complaint were made. If doctors were informed of their over-sights, then underprescription of warfarin may be reduced. Competing interests: None declared |
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Andrew P Davie, Consultant Cardiologist Southern General Hospital, Glasgow. G51 4TF.
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Choudhry et al's paper shows that physicians are less likely to prescribe warfarin for AF after they have treated haemorrhagic complications of warfarin, but not more likely to prescribe warfarin for AF after they have treated thrombo-embolic complications of AF. At first site this is surprising. On second thoughts it is not so surprising. All it shows is that physicians are more easily swayed from a "sin of commission" (prescribing warfarin when things go wrong) than from a "sin of ommission" (not prescribing warfarin when things go wrong). First do no harm, indeed ! Competing interests: None declared |
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Simon P Sanderson, Clinical Lecturer University of Cambridge, Jon Emery, Julian Higgins, and Mark Kroese
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This paper on adverse events and warfarin prescribing raises the question of whether it is possible to identify patients at a high risk of bleeding before treatment is started[1]. Whilst some of this information may be gleaned from the clinical history, physical examination and other phenotypic tests, the use of warfarin in atrial fibrillation may be one example of where pharmacogenetic testing may have a role. Whilst there seems to be little point in performing genetic tests on patients already stabilised on warfarin, the evidence suggests that the early phases of treatment are the most critical and when patients are most vulnerable[2]. A systematic review and meta-analysis of studies investigating the impact of genetic variants of the cytochrome P450 enzyme CYP2C9 and warfarin has shown that patients with these variants require lower daily maintenance doses and are at an increased risk of bleeding[3]. Recent research has also shown that haplotypes of the Vitamin K epoxide reductase gene VKORC1 can stratify patients into low- medium- and high-dose groups and that these haplotypes vary between ethnic groups[4]. Whilst neither of these studies is conclusive, it does perhaps provide one example where pre -prescription pharmacogenetic testing may have a role and should be investigated further – it may help allay the fears of patients and doctors alike. Reference List 1.Choudhry,N.K. et al. Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis. BMJ 332, 141-145 (2006). 2.Higashi,M.K. et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 287, 1690- 1698 (2002). 3.Sanderson,S., Emery,J. & Higgins,J. CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. Genet. Med. 7, 97-104 (2005). 4.Rieder,M.J. et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N. Engl. J. Med. 352, 2285-2293 (2005). Competing interests: None declared |
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Melina Gattellari, Research Fellow School of Public Health & Community Medicine The University of New South Wales, KENSINGTON NSW 2052, John M. Worthington, Nicholas A. Zwar, Sandy Middleton
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Anticoagulation is under-utilised in the treatment of non-valvular atrial fibrillation (NVAF). The study by Choudhry et al (1) suggests that adverse outcomes from anticoagulation have greater influence on the management of NVAF than occurrences of avoidable ischaemic stroke. The authors speculate that this result arises from undue fear or concern about adverse consequences of anticoagulation. We are conducting a representative national survey of 1000 Australian general practitioners (GPs) addressing how fear of anticoagulation affects management of NVAF. Our preliminary findings indicate that aversion to the risk of intracranial haemorrhage was substantial. Doctors are overly cautious in prescribing anticoagulation where there is a perceived risk of major and even minor bleeding even when the benefits of anticoagulation outweigh the risks. In 207 early responses, 45.9% of GPs reported the experience of an ischaemic stroke in their NVAF patients without anticoagulation. Only 13% reported experiencing an intracranial haemorrhage in NVAF patients on anticoagulants. Over half of GPs (54.1%) expected to feel equal responsibility for either an intracranial haemorrhage in a patient on anticoagulants or a fatal or disabling ischaemic stroke without anticoagulation. Nineteen percent would feel more responsible for an intracranial haemorrhage. When asked to select treatment for a hypothetical NVAF patient at ‘high’ risk of stroke (2), 72.5% of GPs would appropriately select warfarin. A perceived risk of bleeding markedly reduced selection of warfarin even when the risk of bleeding was acceptable according to best available evidence (3,4). In the presence of a minor falls risk that would not contraindicate anticoagulation (3) fewer than half of GPs (46.6%) selected warfarin. Only 28% would anti-coagulate the patient at high risk of stroke with a history of recurrent nose-bleeds. Only 20.3% of GPs would anti-coagulate such a patient with a previously treated peptic ulcer bleed. Implementing evidence-based management of NVAF is proving difficult and the potential to reduce stroke risk is yet to be fully realised (5). Our preliminary findings support Choudhry et al’s (1) assertion that there is a profound psychological dimension in the under-prescribing of anticoagulants for NVAF. Any strategy to improve the evidence-based management of NVAF will need to address the excessive concerns clinicians have about anticoagulation. We need to reduce anxiety about ‘acts of commission’ in the management of NVAF. 1. Choudhry NK, Anderson GM, Laupacis A et al. Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis. BMJ 2006; 332; 141-145. 2. Gage BF, Waterman AD, Shannon W, et al Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285:2864-70. 3. Gage BF. Birman-Deych E. Kerzner R. Radford MJ. Nilasena DS. Rich MW. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. American Journal of Medicine. 2005; 118:612-7 4. Man-Son-Hing M et al Choosing anti-thrombotic therapy for elderly patients with atrial fibrillation who are at risk of falls. Archives of Internal Medicine 1999; 159: 677-85. 5. Evans A, Davis S, Kilpatrick C et al. The morbidity related to atrial fibrillation at a tertiary centre in one year: 9.0% of all strokes are potentially preventable. Journal of Clinical Neuroscience 2002; 9: 268-272 Competing interests: None declared |
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