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Rapid Responses: Rapid Responses published:
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Are beta blockers and calcium channel blockers equally good for long term rate control in atrial fibrillation
- Goran Koracevic (24 November 2007)
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There's more to safety than meets the eye
- Magnus I Hird (25 November 2007)
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Rate control in atrial fibrillation
- Gregory YH Lip, Michael Rudolf (28 November 2007)
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Re: Rate control in atrial fibrillation
- Theodora Nikolaidou, Kevin S Channer (4 December 2007)
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Rate control in atrial fibrillation
- Abhay Bajpai, A John Camm, Professor of Cardiology, St George's University of London, SW17 0RE (12 December 2007)
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Re: Rate control in chronic atrial fibrillation
- Theodora Nikolaidou, Kevin S Channer (16 December 2007)
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rate control when atrial fibrillation co-exists with primary hypothyroidism
- oscar,m jolobe (24 January 2008)
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Goran Koracevic, Assist. Prof. , Head for VTE 18000 Nis Serbia
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The recent both thorough and pragmatic editorial simply has to be remembered, although there seems to be the general agreement among physicians that digoxin should be applied to control heart rate in patients with heart failure (HF) / left ventricle (LV) dysfunction.[1] In NICE guidelines, HF has been probably understood as “obvious reason for digitalis as an initial monotherapy”.[2] In ACC AHA ESC 2006 guidelines, digoxin was suggested as Class I (5th recommendation) for rate control in patients with HF / LV dysfunction or sedentary individuals.[3] The same attitude can be found in an important review.[4] The aforementioned is logical, because AF has been recognized risk for HF.[5] The influence of AF upon LV function can be very pronounced, which was very nicely illustrated by Brill as early as in 1938: “It is less commonly appreciated, however, that auricular fibrillation, apart from any other disease of the heart, may cause severe congestive failure and that upon cessation of the arrhythmia, the congestive failure may be followed by complete and lasting recovery.”[6] In practice, I think that one risk factor for rapid decrease of LV functions has been underestimated- diabetes mellitus (DM).[7] Patients with DM are prone to sudden dyspnea, up to pulmonary edema, due to numerous reasons (diastolic / systolic LV dysfunction, induced / worsen by ischemia, DM itself during the long period, acute metabolic worsening, simultaneous arterial hypertension, lung infection, impaired renal function, particularly if with anemia, etc). In addition, DM is very prevalent among acute HF patients (from 27% to 42% ).[8] It is true for acute cardiogenic pulmonary edema, too.[9] Likewise, our choice of a drug for rate control in AF should also reflect our awareness of this fact. On the other hand, there is a potential chance for another mistake in chronic AF treatment. To my opinion, beta-blockers (BBs) and calcium channel blockers (CCBs) should not be treated as equally good options for prolonged rate control in AF. I believe that BBs (indeed, in the absence of contraindications) should be first and CCBs second-line choice for long term rate control. Namely, BBs are indicated for HF therapy (and thus prevention), but CCBs are not. Another advantage of BBs has been also obvious: BBs have been better antiarrhythmics for ventricular rhythm disorders (verapamil has a little role, diltiazem none). Interestingly, sometimes we can still find patients with HF and AF with combination digoxin and verapamil.[10] Such patients may get double benefit from substitution of verapamil with carvedilol (or other BB suggested for HF).[11] Namely, removal of contraindicated verapamil may improve prognosis, and also BBs have been proved to prolong life in HF. Finally, rapid blood pressure (BP) decrease with AF onset has been well- known for the whole century, since experiments almost 100 years ago.[12] It has been less known that we may expect prolonged BP drop in a substantial portion of new-onset AF. Sometimes, previously long-standing arterial hypertension (AHT) disappears for weeks and months following the onset of AF. I named this situation: AF-induced “decapitated” AHT, in analogy with “myocardial infarction –induced “decapitated AHT” (disappearance of AHT following acute myocardial infarction).[13] Thus, we ought to have this limiting factor for BBs and CCBs in mind. References 1.Nikolaidou T, Channer K. Rate control in permanent atrial fibrillation. BMJ 2007;335:1057-1058. 2.National Collaboration Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006. 3.Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: a report of the ACC/AHA task force on practice guidelines and the ESC committee for practice guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation). J Am Coll Cardiol 2006;48:854-906. 4.Lip GY, Tse HF. Management of atrial fibrillation. Lancet 2007;370(9587):604-618. 5.Takata J, Yabe T, Kubo T and Doi Y. Risk Factors for Heart Failure in Patients with Atrial Fibrillation Without Underlying Heart Disease: Gender Difference. J Cardiac Failure 2007;13:S59. 6.Brill IC. Auricular fibrillation with congestive failure and no other evidence of organic heart disease. Am Heart J 1937;13:175–182. 7.Nichols GA, Koro CE, Kolatkar NS. The epidemiology of congestive heart failure in hyperglycemia below the threshold for diabetes: A critical review. Diabetes & Metabolic Syndrome: Clin Res Rev 2007;1:273-278. 8.Alla F, Zannad F, Filippatos G. Epidemiology of acute heart failure syndromes. Heart Fail Rev 2007;12:91-5. Review. 9.Koracevic G, Jankovic R, Stojkovic A. et al. High prevalence of diabetes mellitus among 1098 hospitalized congestive heart failure (CHF) patients. Serb. Congr. Cardiol, Belgrade, 2002. 10.Koracevic G. Benefit from substitution of verapamil with carvedilol in congestive heart failure: theoretical rationale and seven years experience. Kardiol 2003;24(suppl.1): 6. 11.Nieminen MS, Böhm M, Cowie MR. et al. ESC Committe for Practice Guideline (CPG).Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Eur Heart J 2005;26:384-416. 12.Gessel R. A: Cardiodynamics in heart block as affected by auricular systole, auricular fibrillation and stimulation of vagus nerve; Am J Physiol 1916;40:267-313. 13.Koracevic G. Mechanisms and clinical significance of atrial fibrillation - induced “decapitated hypertension”. Mideurop. Congr.Internal Med., Igalo 2001: 67. Competing interests: None declared |
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Magnus I Hird, Pharmacist Practitioner Bloomfield Medical Centre, Blackpool, UK, FY1 6JW
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Nikolaidou and Channer (1) assert that "it is safest to start treatment with digoxin first" in the management of atrial fibrillation. This recommendation appears to be based on the "little evidence that monotherapy with [beta-blockers or rate-limiting calcium-channel blockers] improves heart rate control at rest and during exercise compared with digoxin alone". However at the start of their article they note that in one study there was "no association between achieved ventricular rate and overall survival or quality of life". Instead digoxin seems to be being recommended as a first-line agent for AF on the basis that it "has long been used". The authors note the poor quality of the evidence base on optimal rate-control methods and goals in AF, manifest through small (and likely underpowered trials) not assessing the most appropriate outcomes, and complicated by confounding use of other therapies. However the evidence presented does not seem to infer that digoxin would be superior to beta- blockers, on the contrary if there is an advantage from the efficacy data discussed it would seem to be with the latter. Barber (2) reminds us that therapeutic decisions are a balance of efficacy, safety, patient factors and choice, and cost. Given the lack of good efficacy evidence on which to make a decision and as there is realistically little to choose on the grounds of cost and patient choice (all these drugs can be prescribed in once daily regimens having similar levels of tolerability), then perhaps a decision based on safety would be most appropriate? The authors note a number of safety issues with the alternatives, eg breathlessness, but fail to mention the clear morbidity and mortality benefits beta-blockers have in heart failure (3), a common co-morbid state or complication of AF. Nor do they discuss the safety issues with digoxin, just giving brief mention of "few side effects" and an allusion to the potential for drug interactions. Instead the reality is that digoxin can be a difficult drug to prescribe safely with multiple clinically relevant interactions, a need for dose alteration, especially in renal impairment, and monitoring. It was ranked 8th on a list of medicines responsible for hospital admissions in a recent paper (4) with 2.9% of these events being related to the drug. Although the figure for beta-blockers (6.8%) is higher they are much more widely prescribed so it is likely once the level of patient exposure is taken into account the risk would be higher with digoxin. Whilst it may be that some patients do need more than one drug to sufficiently control their AF in order to minimise symptoms and risk, perhaps it is not safest to start with digoxin? (1) Nikolaidou T, Channer KS. BMJ,2007; 335: 1057-8 (2) Barber N. BMJ, 1995; 310: 923-5 (3) Ko DT, et al. Arch Intern Med, 2004; 164: 1389-94 (4) Pirmohamed M, et al. BMJ, 2004; 329: 15-9 Competing interests: I have been paid by the National Prescribing Centre (an NHS organisation) to produce and deliver educational materials on subjects including Heart Failure and Antithrombotics (including in AF) |
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Gregory YH Lip, Professor of Cardiovascular Medicine City Hospital, Birmingham B18 7QH, Michael Rudolf
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Rate control in atrial fibrillation In their recent Editorial, Nikolaidou and Channer [1] suggest that ‘guidelines on the use of digoxin are inconsistent with evidence from randomised trials’. It would be worth highlighting methodology differences in the published management guidelines for AF. Many guidelines are essentially ‘expert consensus based’; in contrast, the NICE guidelines are based upon systematic reviews and critical appraisal of the literature, following which the evidence is debated by a multidisciplinary guideline development group, which writes the resultant recommendations then undergoes 2 rounds of stakeholder reviews[2]. Their Editorial[1] suggests that no single definition of ideal control of heart rate in chronic atrial fibrillation exists. Current guidelines have defined adequate rate control in AF as maintenance of the ventricular rate response between 60 and 80 beats/min at rest and between 90 and 115 beats/min during moderate exercise, whilst one consensus statement has suggested a target heart rate of <90 at rest and <180 bpm during exercise in AF[3]. However, it is recognized that no controlled clinical trials have fully validated these target rates for preventing all-cause cardiovascular morbidity or mortality, and few data exist that define the most robust method for the assessment of rate control [4]. Indeed, adequate rate control may encompass more than simply the prevention of fast ventricular rates[3]. The Editorial[1] also confuses rate control of AF per se, and the use of digoxin for ancillary conditions, such as associated heart failure. Their summary overview on AF rate control [with no critical appraisal of the various published studies] mixes studies of digoxin monotherapy and combination therapy of digoxin and beta blockers. We would however agree with the Editorial that differences in methodology and outcomes make direct comparisons difficult. In the NICE guidelines, our recommendations on rate control per se are clear[2,3]. We suggest that beta-blockers or rate-limiting calcium antagonists should be the preferred initial monotherapy in all patients. The NICE guidelines do not exclude the use of digoxin, although would suggest that as monotherapy it is probably less good overall for rate control per se - but still useful in predominantly sedentary patients. Where monotherapy gives inadequate rate control (a common situation), the NICE guidelines then recommend combination therapy with beta-blockers or rate-limiting calcium antagonists to be given with digoxin to control the heart rate only during normal activities, whilst rate-limiting calcium antagonists should be given with digoxin to control the heart rate during both normal activities and exercise. Similar conclusions were obtained from a Clinical Evidence systematic review on chronic AF, which had a different systematic review and critical appraisal process[4]. As first line for urgent pharmacological rate control, a Clinical Evidence review also states that intravenous rate- limiting calcium antagonists or beta-blockers should be used[5]. What should be clearly recognized is that digoxin has limited efficacy in hyperadrenergic states such as thyrotoxicosis, fever, acute volume loss, postoperative state and during exertion[6]. Digoxin has many drug interactions and in renal impairment, digoxin toxicity is common. Furthermore, digoxin is no better than placebo for cardioversion, and some evidence suggests that it could make paroxysmal AF worse. In the NICE guidelines, digoxin is not contraindicated, but the evidence – albeit limited – would suggest that beta blockers and rate limiting calcium antagonists would be better for rate control per se. Other comorbidities may give a role for digoxin (eg associated heart failure) but combination therapy is frequently used. Gregory Y H Lip, Clinical Adviser Michael Rudolf, GDG Chair On behalf of the Guideline Development Group for the NICE clinical guideline for the management of atrial fibrillation Corresponding author: Professor GYH Lip University Department of Medicine, City Hospital, Birmingham B18 7QH England, UK. Tel: +44 121 5075080; Fax +121 554 4083; g.y.h.lip@bham.ac.uk 1. Nikolaidou T, Channer KS. Rate control in permanent atrial fibrillation. BMJ 2007;335:1057-1058 2. National Collaboration Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006. 3. Camm AJ, Savelieva I, Lip GY; Guideline Development Group for the NICE clinical guideline for the management of atrial fibrillation. Rate control in the medical management of atrial fibrillation. Heart. 2007;93(1):35-8. 4. Boos C, Lane D, Lip GYH. Atrial fibrillation (chronic). Clinical Evidence 2007; http://clinicalevidence.bmj.com/ceweb/conditions/cvd/0217/0217.jsp 5. Lip GYH, Watson T. Atrial fibrillation (recent onset). Clinical Evidence 2007; http://clinicalevidence.bmj.com/ceweb/conditions/cvd/0210/0210.jsp 6. Li-Saw-Hee FL, Lip GYH. Digoxin revisited. QJM 1998 91: 259-264 7. Falk RH, Leavitt JI. Digoxin for atrial fibrillation: a drug whose time has gone? Ann Intern Med. 1991 Apr 1;114(7):573-5. Competing interests: Gregory Y H Lip is Clinical Adviser; and Michael Rudolf is Chair of the Guideline Development Group for the NICE clinical guideline for the management of atrial fibrillation |
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Theodora Nikolaidou, Research Fellow Royal Hallamshire Hospital, Kevin S Channer
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We thank Lip and Rudolph for their response to our editorial. A number of issues are raised. Currently, the published evidence on rate and symptom management in permanent atrial fibrillation remains limited. For the purposes of the present editorial we have not included full details of our methodology, which will be published in due course. We have critically appraised 57 trials evaluating digoxin, beta-blockers and calcium-antagonists, alone or in combination for rate control in permanent atrial fibrillation. Seven studies were excluded due to weaknesses in methodology or reporting or when obsolete drugs were used. Finally, 50 trials were included of which 25 were double blind, randomised, controlled trials. Lip and Rudolph also argue that our editorial “mixes” studies of digoxin monotherapy and combination therapy. Aiming precisely to avoid this confounding factor, all treatment comparisons in the editorial are made with digoxin monotherapy. We have also clearly identified the evidence on monotherapy and that on combination treatment. Rate control in atrial fibrillation is not an end in itself. It is par excellence a surrogate end point. Patients' symptoms are rarely related directly to rate control. If the main purpose of rate control is to improve the cardiac physiology, this should be associated with improved effort tolerance. The studies clearly do not consistently show this even when rate control has been "improved" with the use of beta-blockers or calcium-antagonists. In the review we did not address emergency treatment of atrial fibrillation. We did not discuss paroxysmal atrial fibrillation either and would agree that digoxin is not helpful in this setting. Our critique of the NICE guidelines is on rate control in permanent atrial fibrillation and the article was clear about this. Finally, guidelines which relegate long-standing treatment can only be justified if there is clear unequivocal evidence of either harm or lack of benefit compared with the proposed alternative. The purpose of our editorial was to highlight the fact that our review of the literature demonstrated neither of these things. Competing interests: None declared |
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Abhay Bajpai, British Heart Foundation Research Fellow St George's University of London, SW17 0RE, A John Camm, Professor of Cardiology, St George's University of London, SW17 0RE
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The recent editorial by Nikolaidou and Channer (1), is confusing and misleads the readers about the evidence-base relating to rate control in patients with chronic atrial fibrillation. They suggest that recent NICE and ACC/AHA/ESC guidelines (2) depart from the historical practice by recommending monotherapy with ß-blockers or rate-limiting calcium antagonists instead of digoxin. The editorial overviews several studies on rate-controlling agents, but without any critical appraisal of these heterogeneous studies. Contrary to their views, both guidelines are consistent in advocating initial monotherapy with either ß-blockers or calcium antagonists based on robust critical analyses of the available evidence. The guidelines do not in any way oust the use of digoxin, but recommend its use predominantly in sedentary patients due to the fact that digoxin will fail to provide adequate control of heart rate during physical activity. While optimal heart rate in atrial fibrillation is not known, a consensus statement has suggested target rates of <90 at rest and <110 during moderate exercise, although no trial has yet looked at morbidity and mortality benefit arising from these target heart rates (3). At present we have only a comparison between two major trials, one in which stricter rate control was used (AFFIRM – Atrial Fibrillation Follow-up Investigation of Rhythm Management) and another in which a more lenient approach to rate control was applied (RACE – RAte Control versus Electrical cardioversion). No difference in major outcome measures was seen (4). The prescription of any rate-controlling medication requires prior assessment of a given patient’s suitability for the medication and knowledge of the contractile state of the myocardium, in addition to whether control of ventricular rate is required at rest as well as during periods of exercise. Both guidelines recommend the use of digoxin as first -line agent for rate-control in patients with heart failure or LV dysfunction. The guidelines also recognise the combination of digoxin with ß-blockers or calcium antagonists in patients inadequately controlled on monotherapy, but the choice of medication needs to be individualised and dose modulated to avoid adverse effects and bradycardia that may arise from the combination. In their editorial the authors refer to a recent sub-study from the AFFIRM trial which showed rate-control with digoxin during exercise was similar to that with ß-blockers, an observation contrary to previously available data (5). The investigators however acknowledge the fact that these similarities between ß-blockers and digoxin may have arisen due to digoxin being primarily given to patients with chronotropic incompetence who had slower initial ventricular response rates. It is also noteworthy that from pooled data, ß-blockers appear to control heart rate on exertion but not at rest, results that can be explained by contribution of weaker ß -blockers or agents with intrinsic sympathomimetic activity to the group analysis. Trials using metoprolol, atenolol, pindolol and nadolol, all controlled heart rates at rest and with exertion. Calcium channel blockers are as effective as ß-blockers for chronic control of heart rates at rest and during exertion. Both ß-blockers and calcium channel blockers should be used with caution in patients with decreased left ventricular function and hypotension. Moreover, for adequate rate control we perhaps need to look further than just mean resting and exercise heart rates, with trials exploring the effect of rate -controlling drugs on irregularity of R-R intervals. Thus, given the available evidence, the current NICE guidance and the ACC/AHA/ESC guidelines 2006 appropriately recommend ß-blockers or rate- limiting calcium antagonists as the preferred initial monotherapy for all patients, and monotherapy with digoxin in predominantly sedentary patients or those with reduced left ventricular function. Where monotherapy is inadequate, combination therapy using modulated doses of digoxin together with beta-blockers or calcium channel blockers should be used. 1. Nikolaidou T, Channer KS. Rate control in permanent atrial fibrillation. BMJ 2007; 335:1057-8 (24 November) 2. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European Society of Cardiology committee for practice guidelines. J Am Coll Cardiol 2006;48:854-906 3. Camm AJ, Savelieva I, Lip GY; Guideline Development Group for the NICE clinical guideline for management of atrial fibrillation.Rate control in medical management of atrial fibrillation. Heart 2007;93:35-8 4. Van Gelder IC, Wyse DG, Chandler ML, Cooper HA, Olshansky B, Hagens VE, Crijns HJ; RACE and AFFIRM Investigators. Does intensity of rate-control influence outcome in atrial fibrillation? An analysis of pooled data from the RACE and AFFIRM studies. Europace. 2006 Nov;8(11):935-42 5. Olshansky B, Rosenfeld LE, Warner AL, Solomon AJ, O'Neill G, Sharma A, et al. The atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study: approaches to control rate in atrial fibrillation. J Am Coll Cardiol 2004;43:1201-8 Competing interests: AJ Camm is a member of the Guideline Development Group for the NICE clinical guideline for the management of atrial fibrillation |
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Theodora Nikolaidou, Research Fellow Royal Hallamshire Hospital, Sheffield, S10 2JF, Kevin S Channer
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We welcome the response of Bajpai and Camm to our editorial.1 They support the NICE guidance2 for monotherapy with beta-blockers or calcium antagonists in chronic atrial fibrillation, despite the lack of evidence for their superiority in exercise tolerance, heart rate variability or 24-hour heart rate. They claim that robust critical analysis has been used by NICE, of which we have seen no evidence. Our systematic review critically appraised the available evidence. Our findings are very clear and not at all misleading. In support of beta-blocker monotherapy Bajpai and Camm claim that “trials using metoprolol, atenolol, pindolol and nadolol all controlled heart rates at rest and with exertion”. This is not supported by the evidence. Out of ten studies assessing beta-blockers on their own, only one (with timolol) shows improved heart rate control at rest compared to digoxin.3 The combination of digoxin with a beta-blocker shows more consistent improvement in heart rate at rest and exercise,3,4,5-15 but often at the expense of worsening exercise tolerance.5-7,9,13 In our analysis of beta-blockers we considered their cardioselective properties and intrinsic sympathomimetic activity. Metoprolol has only been used as monotherapy in one study, 16 which shows no benefit in exercise heart rate or exercise tolerance over digoxin. Two studies tried atenolol on its own.16,17 One reports improvement in exercise heart rate only,17 and neither shows benefit in exercise tolerance. Similarly pindolol on its own has only been used in one study,18 where pindolol and digoxin are equally effective at reducing ambulatory heart rate compared to placebo. There in no available data on nadolol use as monotherapy. Similarly, the claim that “calcium channel blockers are as effective as beta-blockers for chronic control of heart rates at rest and during exertion” is probably true, as equally sparse evidence exists to support this. Only one study has shown diltiazem better than digoxin at controlling heart rate at rest (with high dose diltiazem 360mg/day).19 Diltiazem has not been shown to improve exercise tolerance when used alone. However, in most studies evaluating the combination of diltiazem with digoxin heart rate improves both at rest and during exercise, when compared to digoxin alone. Additionally, several studies report improved 24-hour heart rate control with the combination compared to digoxin.17,20-24 Monotherapy with verapamil has been examined in seven studies and found to improve exercise heart rate compared to digoxin in three. Combination of verapamil with digoxin is shown to improve resting, exercise and ambulatory heart rate. The above evidence does not support the 2006 NICE guidelines for initial monotherapy with beta-blockers or calcium antagonists. NICE seem to have made the mistake of attributing the synergistic effect of combination treatment in the published studies to just the beta-blocker or calcium antagonist used. We believe that the current guidelines are not evidence based and, therefore, not safe. Digoxin, with the addition of a beta-blocker or calcium antagonist as required, should be first line treatment for rate control in chronic atrial fibrillation. 1. Nikolaidou T, Channer KS. Rate control in permanent atrial fibrillation. Bmj 2007;335(7629):1057-8. 2. National Collaboration Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians, 2006. 3. David D, Segni ED, Klein HO, Kaplinsky E. Inefficacy of digitalis in the control of heart rate in patients with chronic atrial fibrillation: beneficial effect of an added beta adrenergic blocking agent. Am J Cardiol 1979;44(7):1378-82. 4. Khand AU, Rankin AC, Martin W, Taylor J, Gemmell I, Cleland JG. Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? J Am Coll Cardiol 2003;42(11):1944-51. 5. Lewis RV, McMurray J, McDevitt DG. Effects of atenolol, verapamil, and xamoterol on heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation. J Cardiovasc Pharmacol 1989;13(1):1-6. 6. DiBianco R, Morganroth J, Freitag JA, Ronan JA, Jr., Lindgren KM, Donohue DJ, Larca LJ, Chadda KD, Olukotun AY. Effects of nadolol on the spontaneous and exercise-provoked heart rate of patients with chronic atrial fibrillation receiving stable dosages of digoxin. Am Heart J 1984;108(4 Pt 2):1121-7. 7. Atwood JE, Sullivan M, Forbes S, Myers J, Pewen W, Olson HG, Froelicher VF. Effect of beta-adrenergic blockade on exercise performance in patients with chronic atrial fibrillation. J Am Coll Cardiol 1987;10(2):314-20. 8. Lundstrom T, Moor E, Ryden L. Differential effects of xamoterol and verapamil on ventricular rate regulation in patients with chronic atrial fibrillation. Am Heart J 1992;124(4):917-23. 9. Myers J, Atwood JE, Sullivan M, Forbes S, Friis R, Pewen W, Froelicher V. Perceived exertion and gas exchange after calcium and beta- blockade in atrial fibrillation. J Appl Physiol 1987;63(1):97-104. 10. Molajo AO, Coupe MO, Bennett DH. Effect of Corwin (ICI 118587) on resting and exercise heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation. Br Heart J 1984;52(4):392-5. 11. Brodsky M, Saini R, Bellinger R, Zoble R, Weiss R, Powers L. Comparative effects of the combination of digoxin and dl-sotalol therapy versus digoxin monotherapy for control of ventricular response in chronic atrial fibrillation. dl-Sotalol Atrial Fibrillation Study Group. Am Heart J 1994;127(3):572-7. 12. Cristodorescu R, Rosu D, Deutsch G, Verdes A, Luca C. The heart rate slowing effect of pindolol in patients with digitalis resistant atrial fibrillation and heart failure. Med Interne 1986;24(3):207-15. 13. Koh KK, Song JH, Kwon KS, Park HB, Baik SH, Park YS, In HH, Moon TH, Park GS, Cho SK, et al. Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in combination with digoxin to control ventricular rate in chronic atrial fibrillation: randomized crossover study. Int J Cardiol 1995;52(2):167-74. 14. Kochiadakis GE, Kanoupakis EM, Kalebubas MD, Igoumenidis NE, Vardakis KE, Mavrakis HE, Vardas PE. Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study. Europace 2001;3(1):73-9. 15. Atwood JE, Myers J, Quaglietti S, Grumet J, Gianrossi R, Umman T. Effect of betaxolol on the hemodynamic, gas exchange, and cardiac output response to exercise in chronic atrial fibrillation. Chest 1999;115(4):1175-80. 16. Tsuneda T, Yamashita T, Fukunami M, Kumagai K, Niwano S, Okumura K, Inoue H. Rate control and quality of life in patients with permanent atrial fibrillation: the Quality of Life and Atrial Fibrillation (QOLAF) Study. Circ J 2006;70(8):965-70. 17. Farshi R, Kistner D, Sarma JS, Longmate JA, Singh BN. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. J Am Coll Cardiol 1999;33(2):304-10. 18. Wang R, Camm J, Ward D, Washington H, Martin A. Treatment of chronic atrial fibrillation in the elderly, assessed by ambulatory electrocardiographic monitoring. J Am Geriatr Soc 1980;28(12):529-34. 19. Roth A, Harrison E, Mitani G, Cohen J, Rahimtoola SH, Elkayam U. Efficacy and safety of medium- and high-dose diltiazem alone and in combination with digoxin for control of heart rate at rest and during exercise in patients with chronic atrial fibrillation. Circulation 1986;73(2):316-24. 20. Maragno I, Santostasi G, Gaion RM, Trento M, Grion AM, Miraglia G, Dalla Volta S. Low- and medium-dose diltiazem in chronic atrial fibrillation: comparison with digoxin and correlation with drug plasma levels. Am Heart J 1988;116(2 Pt 1):385-92. 21. Lewis RV, Laing E, Moreland TA, Service E, McDevitt DG. A comparison of digoxin, diltiazem and their combination in the treatment of atrial fibrillation. Eur Heart J 1988;9(3):279-83. 22. Lundstrom T, Ryden L. Ventricular rate control and exercise performance in chronic atrial fibrillation: effects of diltiazem and verapamil. J Am Coll Cardiol 1990;16(1):86-90. 23. Steinberg JS, Katz RJ, Bren GB, Buff LA, Varghese PJ. Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise. J Am Coll Cardiol 1987;9(2):405- 11. 24. Theisen K, Haufe M, Peters J, Theisen F, Jahrmarker H. Effect of the calcium antagonist diltiazem on atrioventricular conduction in chronic atrial fibrillation. Am J Cardiol 1985;55(1):98-102. Competing interests: None declared |
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oscar,m jolobe, retired geriatrician manchester medical society, c/o john rylands university library, oxford road, manchester M13 9PP
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In the elderly, atrial fibrillation (AF) might co-incidentally co- exist with primary hypothyroidism since both atrial fibrillation(1) and primary hypothyroidism(2) are commoner with increasing age(1)(2). The conseqences of thyroid replacement therapy in that subgroup of patients raise issues different from those raised by the editorial on rate control in a presumably euthyroid population(3).For example, the observation that patients on replacement therapy generally feel at their best when the dosage of thyroxine raises the serum free thyroxine to levels which result in a reduction of thyroid stimulating hormone (TSH) "towards the bottom of the normal range or even a little below it"(4) should be tempered with the recognition that this might incur the side effect of a transition from optimum heart rate to a heart rate which, in turn, might insidiously generate tachycardic cardiomyopathy. The risk of unrecognised overtreatment is compounded by the fact that, in a reference population without risk factors for thyroid disease(including absence of thyroid antibodies)the median and 97.5 centiles for TSH show a progressive and age -related increase in those aged > 70(2). This observation has prompted a study in which the reference population numbered 13,344 subjects, 1669 of whom were aged 70 or more. In that reference population the 95% confidence limits for TSH were 5.24-8.60 mIU/L in the 70-79 age group, and 6.17-10.85 mIU/L in the 80+ age group. According to the authors, the shift in reference range "could either facilitate or be a consequence of healthy ageing or may represent subtle thyroid deficiency that could be either beneficial or deleterious"(5). Accordingly, the balance of benefit vs harm of replacemnent therapy needs to be more carefully calibratedn in those elderly patients in whom AF co-exists with subclinical hypothyroidism and in whom the "healthy" normal range for TSH is not known References (1)Steinberg JS Atrial fibrillation: an emerging epidemic Heart 2004:90:239-240 (2)Hollowell JG., Staehling NW., Flanders WD et al Serum TSH, T4, and thyroid antibodies in the United States population(1988 -1994): National Health and Nutritional Examination(NHANES III). Journal of Clinical Endocrinology and Metabolism 2002:87:489-499 (3)Nikolaidou T., Channer KS Rate control in permanent atrial fibrillation British Medical Journal 2007:335:1057-8 (4) Toft AD., Beckett GJ Thyroid function tests and hypothyroidism British Medical Journal 2003:326:296-7 (5) Surks MI., Hollowell JG Age-specific distribution of serum thyrotropin an d antithyroid antibosies in the US population: Implications for the prevalence of subclinical hypothyroidism Journal of Clinical Endocrinology and Metabolism 2007:92:4575-82 Competing interests: None declared |
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