Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Helicobacter pylori and spironolactone -the duo may be more ulcerogenic?
- Prasanta Padhan (14 July 2006)
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Spironolactone and risk of upper gastrointestinal events
- Asif Raheem, 110062 (16 July 2006)
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Spironolactone and upper G.I. events
- Mohan P Thottatthil (16 July 2006)
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Does spironolactone cause a fall in intramucosal pH?
- Richard G Fiddian-Green (17 July 2006)
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Spironolactone may not be guilty
- Eugene Campbell, Anthony Shonde and Stephen Foley (21 July 2006)
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Spironolactone and risk of upper gastrointestinal events: population based case-control study
- Tilak Ghosh (24 July 2006)
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Author's reply
- Katia M Verhamme, Jeanne P. Dieleman, Bruno HCh Stricker, Miriam CJM Sturkenboom (9 August 2006)
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Spironolactone and risk of upper gastrointestinal events: cause or effect?
- Neeraj Bhala, Mary C. Elliott and Edward Goble (12 August 2006)
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Spironolactone and risk of upper gastrointestinal events: comments
- Jennifer E Stark (12 August 2006)
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Causality schmausality
- Gruffydd P Jones (12 August 2006)
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Spironolactone : Causality of upper gastrointestinal events is not proven
- Shui Hao Chin, Trishna Chakravorty, and Russell C Davis (16 August 2006)
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Spironolactone and liver cirrhosis
- Mario Guslandi (17 August 2006)
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Spironolactone and increased risk of upper gastrointestinal bleeding: an unproven association
- Muhammad F Dawwas (17 August 2006)
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Spironolactone's role is undiminished.
- Edoardo Cervoni (17 August 2006)
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Ulcerogenic medications and H. Pylori are the cause of peptic ulcer.
- Nicholas I Church (27 August 2006)
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Spironolactone in heart failure-severity does matter.
- vinod aiyappan (18 September 2006)
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Prasanta Padhan, MD,SR IN INTERNAL MEDICINE JIPMER,PONDICHERRY,INDIA.605006
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Dear Editor, The study by Katia Verhamme et al show that the risk of gastroduodenal ulcers or upper gastrointestinal bleeding is significantly increased in patients using spironolactone(1).However in their study,the prevalence of Helicobacter pylori infection in these patients who were on spironolactone is not being mentioned.This may be important due to the fact that,H.pylori eradication may at least decrease the risk of gastointestinal bleeding in patients who are on regular treatment with spironolactone. Reference: (1)Verhamme K,Mosis G,Dieleman J,Stricker B,Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study.BMJ 2006; 0: bmj.38883.479549.2Fv1. Competing interests: None declared |
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Asif Raheem, senior registrar cardiology Batra hopsital new delhi, 110062
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Sir, Patients, who may be taking spironolactone, may be high-risk pts for cardiovascular events who may already be taking low dose aspirin for primary/secondary prophylaxis. Studies have shown that patients prone for gastric dyspepsia have a higher tendency to develop gastric erosions even with low dose aspirin use, hence forth these confounding factors need to be evaluated before nailing down spironolactone as one of the culprit. Competing interests: None declared |
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Mohan P Thottatthil, Retired Calicut India 673571
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I've been taking SPIRONOLACTONE at 100mg per day, in divided doses for hyperaldosternism diagnosed in 1992. i find satisfactory relief of the muscular fatige following even mild exercises. but I have not had any signs of a gastrointestinal problem after the long period of drug usage. I am 60 now. My serum K levels are maintained between 4 and 4.5, and i get the electrolytes checked every month. I do not take alcoholic drinks and am a non-smoker and a strict vegetarian all my life.
Competing interests: None declared |
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Richard G Fiddian-Green, None None
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Carbenoxolone sodium was remarkably effective in healing gastric ulcers but was not adopted in clinical practice because of its side effects, weight gain, oedema, hypertension, hypokalaemia and hypernatraemia. The potassium-retaining diuretic amiloride and spironolactone were tested in an effort to prevent these complications. They were effective in preventing the side effects but markedly reduced the ulcer-healing effect of the carbenoxolone sodium (1). Might spironolactone compromise the ulcer healing of carbenoxelone via "sodium intracellular calcium signaling via plasma membrane verapamil-sensitive calcium channels and thereby enhancing the function of the Na(+)/H(+) antiport"(2)? Enhancement of the function of the Na(+)/H(+) antiport should limit the fall in intracellular pH which is the putative final common pathway in the evolution of stress ulceration (3). Might, therefore, spironolactone exert its putative ulcerogenic effects by inducing a fall in intracellular pH? If so how might this be induced? Spironolactone is a specific competitive inhibitor of aldosterone binding to receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. The most important regulator of aldosterone secretion is angiotensin II which is the splanchnic vasoconstrictor implicated in the pathogenesis of stress ulceration (4) and presumed to cause a fall in intramucosal pH (5). In inhibiting aldosterone binding in the distal convoluted tubule might, therefore, spironolactone induce a fall in intramucosal pH by stimulating angiotensin II release either directly or indirectly? There is some evidence that it might (6). 1. PI, Lewis SI, Vincent-Brown A, Holdstock DJ, Gribble RJ, Murgatroyd RE, Baron JH. The influence of amiloride on the therapeutic and metabolic effects of carbenoxolone in patients with gastric ulcer. A double-blind controlled trial. Scand J Gastroenterol Suppl. 1980;65:51-7. 2. Nylander-Koski O, Mustonen H, Puolakkainen P, Kiviluoto T, Kivilaakso E. Epidermal Growth Factor Enhances Intracellular pH Regulation via Calcium Signaling in Acid-Exposed Primary Cultured Rabbit Gastric Epithelial Cells. Dig Dis Sci. 2006 Jul 11; 3. Fiddian-Green RG, McGough E, Pittenger G, Rothman E. Predictive value of intramural pH and other risk factors for massive bleeding from stress ulceration. Gastroenterology. 1983 Sep;85(3):613-20. 4. Bailey RW, Bulkley GB, Hamilton SR, Morris JB, Haglund UH, Meilahn JE. The fundamental hemodynamic mechanism underlying gastric "stress ulceration" in cardiogenic shock. Ann Surg. 1987 Jun;205(6):597-612. 5. Reilly PM, Bulkley GB. Vasoactive mediators and splanchnic perfusion. Crit Care Med. 1993 Feb;21(2 Suppl):S55-68. 6. Keidar S, Gamliel-Lazarovich A, Kaplan M, Pavlotzky E, Hamoud S, Hayek T, Karry R, Abassi Z. Mineralocorticoid receptor blocker increases angiotensin-converting enzyme 2 activity in congestive heart failure patients. Circ Res. 2005 Oct 28;97(9):946-53. Competing interests: Tonometric patents issued in my name. |
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Eugene Campbell, Research Fellow University of Nottingham, NG7 2UH, Anthony Shonde and Stephen Foley
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Editor, Verhamme and colleagues (1) present their data and case for warning patients on spironolactone about an increased risk of upper GI bleeding. They use an electronic database and conditional logistic regression analysis with adjustments. Examining the paper with a pencil, paper and commonsense, we do not believe their conclusion, and will not alter our clinical practice. From a population of 300,000, they identified 523 cases with upper GI events, of which only 13 were currently taking spironolactone. Of these 13, nearly 70% were also on agents known to cause ulcers. Only 30 of the control population were currently taking spironolactone, but these controls were less likely to be taking ulcer- causing drugs. Similarly, the controls overall had significantly less comorbidity than the cases. Despite the efforts of regression analysis, basing a conclusion on such a small number of patients is meaningless. So will we warn patients about a risk of bleeding…….no, not due to spironolactone. But commonsense says they are at increased risk of GI events if they have multiple medical conditions and are on ulcer-causing agents. 1. Katia Verhamme, Georgio Mosis, Jeanne Dieleman, Bruno Stricker, Miriam Sturkenboom BMJ, doi:10.1136/bmj.38883.479549.2F Competing interests: None declared |
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Tilak Ghosh, SpR Gastroenterology Scunthorpe
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Dear sir, The above study was a interesting read. Two points are worth mentioning A)I feel the number of patients who were in the study who used spironolactone(current and past use) and had a GI event was very few(17 i believe).I wonder if with such small number of patients we are justified in drawing any rigid conclusions. B)It would be interesting to know what were the endoscopic findings in those 17 patients who had taken Spironolactnoe in the past or present so that the type of upper GI lesions in Spironolactone users can be assessed. Competing interests: None declared |
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Katia M Verhamme, Senior Researcher Dept of Medical Informatics, Erasmus MC, 3000 DR Rotterdam, The Netherlands, Jeanne P. Dieleman, Bruno HCh Stricker, Miriam CJM Sturkenboom
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Dear editor, With interest, we have read the rapid responses to our article, “Spironolactone and risk of upper gastrointestinal events: population based case-control study"(1) and would like to reply to some of the questions/concerns that have been raised. Dr Padhan suggested that Helicobacter pylori eradication in patients on spironolactone might decrease the risk of gastro intestinal bleeding in those patients treated with spironolactone. We appreciate this suggestion but emphasize that this was not our research hypothesis. As Dr Raheem specified, patients using spironolactone probably also use more acetylsalicylic acid which by itself increases the risk for upper gastrointestinal event.(2) Therefore, we adjusted for acetylsalicylic acid in our final model. Dr Thottatthil commented that he had been taking spironolactone 100 mg for the treatment of hyperaldosteronism and never experienced any gastric discomfort so far. This does not surprise us as the absolute risk of developing a gastrointestinal event on spironolactone, is relatively low due to the low incidence of upper gastrointestinal events in the general population. Dr Green suggested that the association between the use of spironolactone and the occurrence of upper gastrointestinal bleeding might be explained by a fall in the intramucosal pH. This is an interesting hypothesis that of course can not be answered by observational research. Dr Campbell et al. questioned the validity of our study and the conclusions we drew as the number of exposed cases was low and as cases had more comorbidity than controls. Low numbers, however, are a precision issue rather than an argument against validity. The fact that cases had more morbidity than controls is not surprising but can be adjusted for in the analysis. We disagree that conclusions based on small numbers are meaningless. Our study is not the first to report on this association, there have been case reports, a clinical trial, and recently a retrospective cohort study on the side effects of spironolactone in 762 patients has been published where it was shown that gastritis was reported in 2% of all patients. (3) Finally, we appreciate the suggestion of Dr Ghosh to study the type of upper gastrointestinal lesions in spironolactone users and to study specific patterns, but we do believe that this type of research is better done in the hospital with access to the complete endoscopic reports rather than in a general practice database. References: 1. Verhamme K, Mosis G, Dieleman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ 2006 2. Weil J, Langman MJ, Wainwright P, Lawson DH, Rawlins M, Logan RF, et al. Peptic ulcer bleeding: accessory risk factors and interaction with non-steroidal anti-inflammatory drugs. Gut 2000;46:27-31 3. Williams E, Katholi R, Karambelas M. Use and side-effect profile of spironolactone in a private cardiologist’s practice. Clin Cardiol 2006;29:149-53. Competing interests: None declared |
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Neeraj Bhala, Specialist Registrar in Gastroenterology & General Medicine University Hospital of Coventry & Warwick, Walsgrave, Coventry, UK, CV2 2DX, Mary C. Elliott and Edward Goble
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Verhamme and colleagues deserve praise for the impressive number of confounding variables they have accounted for in their recent study.1 Whilst they argue that spironolactone per se potentially leads to an increased risk of upper gastrointestinal bleeding events, we would contend that this could be an effect of underlying pathology rather than the medication itself. Out of 306,645 patients and 523 bleeds, only 13 patients were on spironolactone therapy (0.0042% and 2.5% respectively) and hence we feel a more cautious interpretation is required. Furthermore, these investigators assert ‘a strong dose-response relationship was seen’, which is difficult to ascertain when comparing only six high dose to seven low dose cases. With such small figures, an overall odds ratio of 2.7 (95% confidence interval 1.2-6.0) only just becomes statistical significant. In clinical practice, the major clinical indications for spironolactone will be congestive cardiac failure and ascites complicating chronic liver disease, with the latter expressly excluded in this study. In previous population-based studies, heart failure was an even more impressive accessory risk factor for bleeds (odds ratio 5.9, 95% CI 2.3- 13.1).2 This underlies its inclusion in upper gastrointestinal haemorrhage risk stratification scores.3 The authors also point out biologically plausible mechanisms by which aldosterone antagonism could be implicated, although we note that the cited case reports date back to the 1970’s. This highlights a paucity of published material, both in clinical practice and the underlying pathophysiology. As well as heart failure, could there be another confounder, such as Helicobacter pylori? Like any therapy, spironolactone has side effects. However, it has an important role to play in a number of conditions, including a 30% mortality benefit in severe heart failure.4 This needs to be borne in mind before drawing conclusions of population risk that, despite efforts, may be artefactual rather than causal. 1. Verhamme K, Mosis G, Dieleman J, Stricker B, and Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ 2006 2. Weil J, Langman MJ, Wainwright P, Lawson DH, Rawlins M, Logan RF, Brown TP, Vessey MP, Murphy M, Colin-Jones DG. Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut. 2000 Jan;46(1):27-31. 3. Rockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJ 1995;311:222–6. 4. Pitt B., Zannad F., Remme W. J., Cody R., Castaigne A., Perez A., Palensky J., Wittes J., The Randomized Aldactone Evaluation Study Investigators. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. N Engl J Med 1999; 341:709-717, Sep 2, 1999. Competing interests: None declared |
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Jennifer E Stark, Assistant Professor University of Oklahoma College of Pharmacy73117
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The authors have not addressed an important confounding variable that could be responsible for the increased bleeding event rate observed in the patients prescribed spironolactone in their case-control study.(1) The study did not consider ascites secondary to hepatic cirrhosis as a potential confounder. While excluding patients with a history of alcohol misuse, the authors cannot exclude other causes of cirrhosis (e.g. viral hepatitis). Patients with decompensated cirrhosis are inherently at increased risk of bleeding events given their concomitant coagulapathy due to decreased production of clotting factors by the liver as well as esophageal varices related to portal hypertension. The authors’ observed dose response relationship seen with increasing spironolactone doses and gastrointestinal events suggests those patients could have been prescribed spironolactone for treatment of ascites. The recommended dosing of spironolactone for ascites is 50 mg to 400 mg daily (2) in contrast to the dose of spironolactone recommended for use in heart failure of 12.5 mg to 50 mg daily.(3) Without controlling for this important variable, one cannot conclude that spironolactone was the cause of increased gastrointestinal bleeding events. 1. Verhamme K, Mosis G, Dielman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ 2006; 333:330-33. 2. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004; 350:1646-54. 3. The task force for the diagnosis and treatment of CHF of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure (update 2005). www.escardio.org/knowledge/guidelines/ Chronic_Heart_Failure.htm (accessed 2006 Aug 11). Competing interests: None declared |
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Gruffydd P Jones, General practitioner Meddygfa Waunfawr, Caernarfon, Gwynedd LL55 4YY
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I can only draw one certain conclusion from this piece of research: it is unwise to ascribe causality to an association demonstrated by a case control study. The authors have shown that people who get gastrointestinal (GI) bleeds are 4.6 times more likely to be taking spironolactone than those who don't get GI bleeds. Does this mean that spironolactone causes GI bleeding? Well if it does, then antacids (odds ratio 3.52) must also cause GI bleeding. And PPIs and H2 antagonists (odds ratio 2.83) must be more likely to cause GI bleeding than aspirin or anticoagulants (odds ratio 2.16 for both). There are two possible explanations for the authors’ findings: 1. Spironolactone causes GI bleeding and 2. People who are given spironolactone are inherently more likely to get GI bleeding. The authors have tried to compensate for the known risk factors for GI bleeding, but have they identified them all? In my own practice, spironolactone is used rarely, exclusively in heart failure, and particularly in difficult heart failure patients who are intolerant of ACE -inhibitors and AII-blockers or prone to hypokalaemia. Was there a difference in potassium values or creatinine values between cases and controls? Doesn't renal function influence the risk of GI-bleeding and affect the serum levels of a host of drugs? To be fair, the authors do not openly argue that there is a causal relationship but they imply it the last sentence of their paper (...patients should be informed about the potential of upper gastrointestinal events when using spironolactone). If I were to tell a patient "Did you know that people taking spironolactone are more likely to get bleeding ulcers?" they would assume that they could lower the risk by stopping the drug. They shouldn't. Nor should we. There is, after all, an association between height and baldness (confounding factors age and sex) but shaving your head does not make you taller. In fact, it makes you slightly shorter.1 References: 1. Personal observation Competing interests: None declared |
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Shui Hao Chin, Registrar in Cardiology Sandwell and West Birmingham Hospitals NHS Trust, Lyndon, West Bromwich B71 9HQ, Trishna Chakravorty, and Russell C Davis
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EDITOR – The discovery of a dose-dependent association between spironolactone and gastrointestinal bleeding by Verhamme et al must have caused a stir in the world of internal medicine. This conclusion was drawn from a population based case-control study which derived its data between 1996 and 2003. Interestingly RALES1 was published in 1999, establishing the central role of spironolactone in treatment of severe heart failure. According to Verhamme et al, spironolactone was associated with a 2.7 -fold increase in upper gastrointestinal events, the association being strongest in patients taking the higher doses. In RALES, 12.5mg, 25mg and up to 50mg of spironolactone was used and there were no statistical difference in the incidence of gastrointestinal events between the treatment arm and the placebo arm. Standard doses of spironolactone in treatment of hypertension and ascites in cirrhosis are up to 400mg; the authors should therefore clarify what they considered to be a ‘defined daily dose’. Diagnoses of heart failure in primary care are often incorrect,2 but patients prescribed spironolactone are more likely to have had severe left ventricular dysfunction confirmed by echocardiography, as it is only in patients with confirmed severe systolic dysfunction and persistent symptoms that spironolactone is indicated. Considering diuretic dose alone is unlikely to exclude confounding for severity of heart failure, therefore. The situation echoes one in hypertension in the mid-1990’s, when the use of dihydropyridine calcium antagonists in hypertension was reported to be associated with increased mortality,3 and there were calls for use of these drugs to be restricted.4 Subsequent randomised trial data have proven the efficacy and safety of dihydropyridine treatment,5 which is actually superior to older medication. It is important that an unconfirmed theory generated by observational data should not prevent patients benefiting from the major prognostic benefit of spironolactone in severe heart failure. 1Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med 1999; 341:709-17. 2Remes J, Miettinen H, Reunanen A, Pyorala K. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J 1991;12:315 -21. 3Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 1995;92:1326-31. 4Furberg CD, Psaty BM. Calcium antagonists: not appropriate as first line antihypertensive agents. Am J Hypertens 1996;9:122-5. 5Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895-906. Competing interests: None declared |
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Mario Guslandi, Gastroenterology Unit- S.Raffaele University Hospital Via Olgettina 60- 20132 Milan, Italy
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Spironolactone is commonly used in decompensated liver cirrhosis to either prevent or treat ascites formation. Most patients ,due to <a href="http://www.ntsearch.com/search.php?q=portal&v=55">portal</a> hypertension, have either oesophageal varices or congestive gastropathy or both, which represent recognized ,possible causes of upper GI bleeding. In Verhamme's paper no data are provided about the possible co-existence of advanced liver disease, in particular liver cirrhosis, among the subjects who reportedly underwent upper GI bleeding without showing evidence of gastric or duodenal ulcers. The lack of information on the concomitant presence of oesophageal varices and/or congestive gastropathy as possible sources of bleeding makes it hard to draw conclusions about a causal role of spironolactone. Competing interests: None declared |
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Muhammad F Dawwas, Clinical Research Fellow Clinical Effectiveness Unit, The Royal College of Surgeons of England, WC2A 3PE
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Although Verhamme et al's study of the association between spironolactone use and risk of upper gastrointestinal bleeding (1) is an interesting one, it has a number of noteworthy limitations. Firstly, the mortality benefit conferred by spironolactone therapy in heart failure has only been demonstrated among patients with severe disease (2) and hence, as the authors rightly acknowledged, such patients are far more likely to be prescribed this therapy than those with, for example, relatively asymptomatic echocardiographic evidence of impaired left ventricular function. Given the fact that the authors neither stated the criteria by which they defined heart failure, an important consideration in any primary care-based study (3), nor reliably adjusted for its severity in the risk model, it is plausible that the observed higher risk of upper gastrointestinal bleeding among spironolactone users is explicable by a preponderance of severe heart failure in this group. Secondly, the study made no attempt to examine or adjust for the confounding effect of Helicobacter Pylori infection, a crucial player in the pathogenesis of peptic ulcer disease (4), leaving its findings open to the criticism that they may simply be due to a higher prevalence of H. Pylori among those with gastroduodenal ulcers. Thirdly, notwithstanding the exclusion of those with oesophageal varices and alcoholism from the study, it is still possible that it included some patients with chronic liver disease. In view of the well- established significantly increased risk of peptic ulcer disease among cirrhotics (5), many of whom are regular consumers of spironolactone, it is conceivable that the observed association between this drug and upper gastrointestinal bleeding may well reflect a higher prevalence of cirrhosis among those who bled while taking the drug, a possibility which was not taken into account in the risk adjustment. Given the above shortcomings, the authors’ conclusion, that spironolactone therapy increases the risk of gastroduodenal ulcers and upper gastrointestinal bleeding, remains unproven and their recommendation to caution patients and doctors about this potential complication should therefore await verification in a more robust risk-adjusted analysis. 1.Verhamme K, Mosis G, Dieleman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ. 2006; 333:330 2.Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med 1999; 341:709-17 3.Sparrow N, Adlam D, Cowley A, Hampton JR. The diagnosis of heart failure in general practice: implications for the UK National Service Framework. Eur J Heart Fail. 2003; 5:349-54 4.Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002; 347:1175-86 5.Saad RJ, Chey WD. Peptic ulcer disease in patients with chronic liver disease: looking beyond bugs and drugs. Gastrointest Endosc. 2005; 62:357-9 Competing interests: None declared |
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Edoardo Cervoni, Primary Care Doctor West Lancashire PCT
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I subscribe the caveats expressed by Eugene Campbell and,I add,Ms Verhamme's reply doesn't diminish at all their validity. The results published in the well known paper by Pitt B et et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. (NEJM 1999; 341:709-17), may instead reinforce the positive role of Spironolactone especially in those patients that Verhamme and Colleagues may have found to be at higher risk of upper GI bleeding. While acknowledging the complexity of this matter in view of the several confounding factors, I do not think this study did enough to elimnate, or reduce them to an acceptable level. As such, the warnings of Dr Verhamme's study may be misleading. Competing interests: None declared |
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Nicholas I Church, Consultant Gastroenterologist Queen Margaret Hospital Dunfermline. KY12 0SU
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Editor The recent study by Verhamme et al. concludes that the use of Sprionolactone is associated with a 2.7 fold increased risk of upper GI events. (1) The authors identified 523 cases and 5230 controls. However, only 13 of the cases were actually using spironolactone. Of these, 9 were also using an ulcerogenic drug. Therefore, the conclusions of the study are actually based on 4 patients who were using Spironolactone alone and suffered an upper GI event. The type of event is also important when considering the clinical relevance of the study. Were the 4 patients found to have minor antral erosions after complaining of abdominal discomfort, or did they have torrential bleeding from posterior duodenal ulcers? The H. Pylori status of the study group is a vital potential confounder which has not been addressed. I would suggest that no useful conclusion can be drawn from a study with such small numbers and confounding factors. 1. Verhamme K, Mosis G, Dielman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population based case-control study. BMJ 2006; 333:330-33. Competing interests: None declared |
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vinod aiyappan, Senior SHO, Medicine Neath port talbot Hospital, Port talbot, SA12 7BX
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I found the article’Spironolactone and risk of upper gastrointestinal events: population based case-control study’ very interesting and relevant in the current world where we have a significant population surviving most insults to the heart and living to a ripe old age. But I think the authors assumption that confounding by severity is unlikely is questionable. In the present day management of congestive Cardiac Failure, spironolactone is added when the response to loop diuretics is not adequate (in other words when the heart failure is severe). These patients are more likely to have congestive gastropathy as a result of heart failure and are more prone for gastrointestinal bleeds than people with mild heart failure. Hence this association need to be looked into more closely, preferably by correlating echocardiographic findings of the patients on spironolactone with the incidence of gastro intestinal bleeds, to see whether spironolactone use is independently associated with adverse gastrointestinal events. Competing interests: None declared |
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