Appraisal Consultation Document - Dual Chamber Pacing
Appraisal Consultation Document
Dual-chamber pacemakers for symptomatic bradycardia due to sick sinus syndrome and/or atrioventricular block
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The Department of Health and the National Assembly for Wales have asked the National Institute for Clinical Excellence (NICE or the Institute) to conduct an appraisal of dual-chamber pacemakers and provide guidance on their use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of dual-chamber pacemakers for the treatment of symptomatic bradycardia due to sick sinus syndrome and/or atrioventricular block. This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, www.nice.org.uk). Note that this document does not constitute the Institute's formal guidance on this Technology. The recommendations made in Section 1 are preliminary and may change after consultation. The process the Institute will follow after the consultation period is summarised below. For further details, see the Guide to the Technology Appraisal Process (this document is available on the Institute's website, www.nice.org.uk).
The key dates for this appraisal are: Details of membership of the Appraisal Committee are given in Appendix A and a list of the sources of evidence used in the preparation of this document is given in Appendix B. |
| Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. |
| This guidance refers only to pacing for the primary indications of sick sinus syndrome and/or atrioventricular block, and does not deal with more complex pacing indications involving bradycardia for other indications considered, such as after cardiac transplantation or where there are intermittent tachycardias, or pacing specifically for advanced heart failure. | |
| 1 | Appraisal Committee's preliminary recommendations |
| 1.1 |
Dual-chamber pacing is recommended as an alternative to single-chamber pacing for the management of symptomatic bradycardia associated with sick sinus syndrome, atrioventricular block, or a combination of sick sinus syndrome and atrioventricular block, except in the following circumstances, where it may not be clinically appropriate.
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| 2 | Clinical need and practice |
| 2.1 | Abnormal heart rhythms are caused by disturbances in electrical impulse generation or its conduction between chambers of the heart principally within the sinus node, atrioventricular (AV) node and the His-Purkinje network. Dysrhythmias may be fast (tachyrhythmias) or slow (bradyrhythmias), and regular or irregular. |
| 2.2 | Symptoms of bradycardia include faints, falls, dizziness and confusion (manifestations of hypotension), palpitations, fatigue on exertion, difficulty with breathing (dyspnoea) and chest pain. The majority of bradycardias are caused by sick sinus syndrome and atrioventricular block |
| 2.3 | Sick sinus syndrome (also known as sinus node dysfunction) is an irreversible dysfunction of the sinus node, a small area of the right atrium in which a small group of cells spontaneously depolarise and act as the heart's natural pacemaker. Sick sinus syndrome is characterised by impaired impulse formation, which is often the result of chronic fibrotic degeneration or calcification of the sinus node and/or the surrounding atrial tissues. |
| 2.4 | Atrioventricular block is a failure in the conduction of electrical impulses from the atria to the ventricles, caused by defects in the AV node, which is situated between the atria and ventricles. The AV node captures waves of depolarisation from the atria, which are then transferred to the ventricles via the bundles of His and the Purkinje system (branches of the conducting system). Atrioventricular block (or heart block arising in the right or left bundles of His) may be intermittent or permanent, and can progress from minimal asymptomatic conduction delay to the ventricles (first degree), to partial (second degree) or complete (third degree) heart block. In complete heart block (also known as complete atrioventricular block) there is no electrical conduction between the atria and ventricles. Although second-degree block is usually asymptomatic it carries a high risk of progression to complete heart block. |
| 2.5 | The diagnosis of sick sinus syndrome and atrioventricular block is based on the correlation of symptoms with electrocardiographic findings (electrocardiogram [ECG] and ambulatory ECG or Holter monitoring). The prognosis of individuals with sick sinus syndrome or atrioventricular block is variable and difficult to predict because it may depend on the presence and severity of comorbitidies (such as ischaemic heart disease), and the underlying cause of the conduction defect. |
| 2.6 | The prevalence of sick sinus syndrome is thought to be approximately 0.03% of the whole population, and estimates of the prevalence of atrioventricular block based on clinical studies range from 0.015 to 0.1%, although it is common for people to have co-existing abnormalities of both the sinus node and the AV node. |
| 2.7 | Pacemakers are indicated for use in the treatment of symptomatic bradycardia, and control or replace the heart's intrinsic electrical activity. Some patients require intermittent pacing, whereas patients whose intrinsic heart rate is slow for most of the time require a pacemaker to pace most of the beats. |
| 2.8 | Pacing systems are electrical devices that consist of a small battery-powered generator and one or more pacing leads that are in contact with the inner wall of the right atrium and/or the right ventricle. The pacemaker senses whether an intrinsic depolarisation has occurred. When this does not occur the pacemaker generates an electrical impulse, which is delivered to the heart muscle, via the pacemaker leads, to initiate contraction. |
| 2.9 | Pacemakers may be broadly classified as single- or dual-chamber devices, depending on whether leads are applied to one or two heart chambers. A range of additional features is also available such as rate modulation, which refers to the ability of pacemakers to increase the pacing rate in response to physical activity or metabolic demand. |
| 2.10 | The British Pacing and Electrophysiology Group (BPEG) and the North American Society of Pacing and Electrophysiology have developed nomenclature that describes the different types of pacemakers (see Appendix D). The BPEG has also developed guidelines on the recommended pacing modes for different underlying conditions (see Appendix E). |
| 2.11 | Single-chamber ventricular pacing has long been used, and is still considered to be the most clinically appropriate treatment for atrioventricular block in the presence of chronic atrial fibrillation. |
| 2.12 | If single-chamber ventricular pacemakers are used in patients with functional atria, some may develop pacemaker syndrome. This refers to a group of symptoms that includes distress, nausea, palpitations, chest pain, fatigue, breathlessness, pre-syncope and syncope. The underlying cause of pacemaker syndrome is not fully understood. It is thought to be caused by loss of the heart's natural AV rhythm causing simultaneous contraction of the atria and ventricles. Under these circumstances blood in the arterial chamber is not efficiently expelled into the ventricles, resulting in large reductions in systolic blood pressure and cardiac output. Patients with severe pacemaker syndrome require an upgrade to a dual-chamber pacemaker. |
| 2.13 | Dual-chamber pacing, and single-chamber atrial pacing (in patients with sick sinus syndrome without atrioventricular block), as opposed to single-chamber ventricular pacing, are considered to be ?physiological' pacing modes because AV synchrony is maintained and the timing of contractions of the atria and ventricles mimics the heart's natural rhythm. |
| 2.14 | Single-chamber atrial pacing is used in the treatment of sick sinus syndrome without atrioventricular block because it preserves natural AV synchrony. Single-chamber ventricular pacing is not recommended in national guidelines for this indication. A few people who receive single-chamber atrial pacemakers go on to develop atrioventricular block, and subsequently require ventricular pacing using a dual-chamber or single-chamber ventricular pacemaker. |
| 2.15 | In the UK, about 26,000 pacemakers are implanted each year. In 2003, 59% of implants were dual-chamber pacemakers, 40% were single-chamber ventricular pacemakers and 1% were single-chamber atrial pacemakers. The average age of the recipients of pacemakers was 76 years. |
| 3 | The technology |
| 3.1 | Dual-chamber pacemakers have pacing leads in the right atrium and ventricle, and BPEG guidelines recommended them for use in people who have atrioventricular block in the absence of chronic atrial fibrillation, and people who have sick sinus syndrome with atrioventricular block. Potential benefits of dual-chamber pacemakers include a reduction in the incidence of pacemaker syndrome and of atrial fibrillation |
| 3.2 | The Association of British Healthcare Industries (ABHI) has advised that the average market (discounted) price of dual-chamber pacemakers is between £1265 (for DDD models) and £1713 (for DDDR), excluding VAT, compared with between £658 (for VVI) and £935 (for VVIR) for single-chamber pacemakers, and leads are £169, excluding VAT (See Appendix E for definitions of device types). The Institute does not have access to the current list price of individual pacemakers. The Institute believes that these market prices represent a substantial discount on the list price of these devices, and these prices may change over time due to environmental factors. |
| 4 | Evidence and interpretation |
| The Appraisal Committee considered evidence from a number of sources (see Appendix B). | |
| 4.1 | Clinical effectiveness |
| 4.1.1 | Outcomes against which the relative effectiveness of dual-chamber and single-chamber pacing were assessed included pacemaker syndrome, exercise capacity, functional status, quality of life (QoL), incidence of atrial fibrillation, stroke, heart failure, mortality and adverse events. |
| Dual-chamber pacing versus single-chamber ventricular pacing | |
| 4.1.2 | Literature searches identified 32 studies of dual-chamber pacemakers versus single-chamber ventricular pacemakers. Four parallel RCTs randomised a total of 7006 patients to single- or dual-pacing modes (MOST and PASE studies), or single- or dual-chamber devices (CTOPP and the UKPACE study). The CTOPP study compared ?physiological' pacing (that is single-chamber atrial pacing for patients with sick sinus syndrome only, or dual -chamber pacing in patients with atrioventricular block) with single-chamber ventricular pacing. Crossover trials (n = 28) randomised a total of 515 patients with sick sinus syndrome and/or atrioventricular block to dual -chamber pacing or single-chamber ventricular pacing. |
| 4.1.3 | Populations in the four parallel RCTs varied between patients with sick sinus syndrome with or without atrioventricular block (MOST), those with atrioventricular block alone (UKPACE), and mixed populations of patients with sick sinus syndrome and atrioventricular block (PASE and CTOPP). |
| 4.1.4 | There was no statistically significant difference in the incidence of mortality or stroke with dual-chamber pacing compared with single-chamber ventricular pacing in the four large RCTs. |
| 4.1.5 | The incidence of atrial fibrillation associated with dual-chamber pacing compared with single-chamber ventricular pacing varied in the four large RCTs. The cumulative incidence of atrial fibrillation was up to 21.4% in the dual-chamber pacing arm, and 27.1% in the single-chamber ventricular pacing arm. The reduction in the relative risk of atrial fibrillation with dual-chamber pacing reached significance in two of the studies (MOST: adjusted hazard ratio, 0.77; 95% confidence interval [CI] 0.64 to 0.92; and CTOPP: annual reduction in relative risk, 27.1%; 95% CI, 5.5 to 43.6%). Meta-analysis of the results of the three RCTs (excluding the UKPACE study) demonstrated a statistically significant reduction in the incidence of atrial fibrillation with dual-chamber pacing (odds ratio, 0.76; 95% CI, 0.65 to 0.90). Meta-analysis incorporating the results of the UKPACE trial were also made available, in confidence, to the Appraisal Committee. |
| 4.1.6 | The MOST study had the highest power to detect differences in the incidence of atrial fibrillation with dual-chamber pacing and single-chamber ventricular pacing because it was a large trial in patients with sick sinus syndrome (thought to be one of the risk factors for atrial fibrillation), and the patients in this study had the highest incidence of prior non-chronic atrial fibrillation (up to 47%), which is also a risk factor for recurrence. The MOST study also reported a statistically significantly higher incidence of atrial fibrillation with pacemaker dependency (compared with pacemaker non-dependency) of 1% with dual-chamber pacing (95% CI, 0.2 to 1.8%; p = 0.01) and 0.7% with single-chamber ventricular pacing (95% CI, 0 to 1.4%; p = 0.04) for every 1% increase in the proportion of ventricular beats paced. A potential confounding factor in RCTs of a mixed population of patients with sick sinus syndrome and with atrioventricular block was that the results from the two populations could not be disaggregated. |
| 4.1.7 | Two out of three studies that reported the rate of heart failure with dual-chamber pacing and single-chamber ventricular pacing reported a lower incidence of heart failure with dual-chamber pacing (which reached significance in one of the studies). Results of the meta-analysis of the two studies (excluding the UKPACE study) showed no overall difference in the rate of heart failure with dual-chamber pacing compared with single-chamber ventricular pacing (pooled odds ratio, 0.83; 95% CI, 0.66 to 1.05). Meta-analysis incorporating the results of the UKPACE trial were also made available, in confidence, to the Appraisal Committee. |
| 4.1.8 | Meta-analysis of the 20 crossover studies showed a statistically significant standardised mean improvement in exercise capacity of 0.35 (95% CI, 0.17 to 0.52; p < 0.001) with dual-chamber pacemakers compared with single-chamber ventricular pacemakers. This was only significant when dual-chamber pacemakers were compared with non-rate-responsive single-chamber ventricular pacemakers; there was no statistically significant difference between DDD and VVIR pacing modes (standardised mean difference 0.11; 95% CI, -0.15 to 0.37). Meta-analysis of exercise capacity with dual-chamber pacing compared with single-chamber ventricular pacing, in patients younger and older than 75 years, demonstrated no difference in exercise capacity for patients older than 75 (standardised mean difference 0.19; 95% CI, -0.08 to 0.45), and significant standardised mean improvement of 0.47 (95% CI, 0.21 to 0.73) for patients younger than 75. Meta-analysis of perceived exercise capacity reported in eight crossover studies showed a statistically significant improvement with dual-chamber pacing (standardised mean improvement 0.68; 95% CI, 0.29 to 1.08). |
| 4.1.9 | Meta-analysis of 12 studies reporting global measures of QoL, using visual analogue scales, showed a statistically significant improvement with dual-chamber pacing compared with single-chamber ventricular pacing. Three of the four RCTs evaluated QoL using the SF-36 (UKPACE data on QoL was not available for the Assessment Report). Statistically significant improvements in QoL with dual-chamber pacing were demonstrated in some of the domains in MOST (improvement in physical function, physical role, social function, energy and emotional role, but not in mental health, pain and general health) and in PASE (improvement in social function, physical role, emotional role, mental health and energy in the short-term). The statistically significant improvements were, however, transient. CTOPP did not report any difference in QoL between dual-chamber and single-chamber pacing using the SF-36, but did report benefit using the SF-6 and QLAP QoL questionnaire. |
| 4.1.10 | There were large variations in the incidence of pacemaker syndrome with single-chamber ventricular pacing reported in the four large RCTs. The incidence reported in trials of pacing mode ranged from 18.3 to 26.1%, whereas trials of pacing device reported the rate of upgrade from single -chamber ventricular pacing to dual-chamber pacing as a result of pacemaker syndrome as approximately 4%. Meta-analysis (based on the assumption that pacemaker syndrome does not occur in dual-chamber pacing) of the three RCTs (excluding the UKPACE study) showed a statistically significant reduction in the incidence of pacemaker syndrome with dual-chamber pacing compared with single-chamber ventricular pacing. This was confirmed by the pooled analysis of 14 crossover studies, which reported a statistically significant improvement in the symptoms of pacemaker syndrome with dual-chamber pacing (standardised mean difference -0.88; 95% CI, -1.13 to -0.62). Meta-analysis incorporating the results of the UKPACE trial were also made available, in confidence, to the Appraisal Committee. |
| Dual-chamber pacing versus single-chamber atrial pacing | |
| 4.1.11 | Literature searches identified one small parallel RCT and two crossover RCTs that randomised a total of 211 patients with sick sinus syndrome to dual-chamber pacing or single-chamber atrial pacing. The parallel RCT was underpowered because this study was a pilot study for a larger trial, and recruitment to the pilot study was suspended before the target number of patients was reached. |
| 4.1.12 | The parallel RCT reported a statistically significantly lower incidence of atrial fibrillation with single-chamber atrial pacing compared with dual-chamber pacing (7.4% for single-chamber atrial pacing; 20% for dual-chamber pacing, p = 0.03), but no statistically significant difference in mortality (all-cause or cardiovascular mortality), in the incidence of heart failure or stroke, functional status (based on specific activity scale scores) or in QoL. |
| 4.1.13 | One crossover study in 19 patients showed a statistically significant improvement in exercise tolerance based on bicycle ergometer tests with single-chamber atrial pacing compared with dual-chamber pacing (single-chamber atrial pacing 103 watts, SD 31, compared with dual-chamber pacing 96 watts, SD 27; p < 0.05). |
| 4.1.14 | The incidence of development of atrioventricular block in patients who received single-chamber atrial pacing was variable, ranging from an annual incidence figure of 1.9% in the parallel RCT to a prevalence of 37% found during follow up in one of the crossover studies. |
| 4.1.15 | The crossover studies reported no difference in the presence of symptoms of cardiac dysfunction (palpitations, dizziness, chest pain) with dual-chamber pacing compared with single-chamber atrial pacing. |
| 4.2 | Cost effectiveness |
| 4.2.1 | Literature searches identified one systematic review of the cost effectiveness of dual-chamber pacing in patients with sick sinus syndrome, sick sinus syndrome with atrioventricular block and unspecified bradycardia who were eligible for dual-chamber or single-chamber pacing. The studies included in this review were of limited relevance because they did not incorporate effectiveness data from the large parallel-group RCTs, because results were not presented as cost per quality adjusted life year (QALY), and because of the technological developments in dual-chamber pacing that have occurred since the publication (in 1996) of the most recent of the papers included. |
| 4.2.2 | Three models were submitted to NICE by consultees and the Assessment Group also developed two separate Markov models that compared dual-chamber with single-chamber pacing according to whether the underlying cause of bradycardia was sick sinus syndrome or atrioventricular block. |
| 4.2.3 | ABHI submitted a discrete event simulation model of the costs and outcomes of DDDR compared with VVIR pacemakers in patients with sick sinus syndrome or atrioventricular block over a 5-year time horizon. Dual-chamber pacing was associated with an incremental cost of £42 and incremental benefits of 0.09 QALYs, to give an incremental cost effectiveness ratio (ICER) of £477 per QALY. Sensitivity analysis demonstrated that the incidence of severe pacemaker syndrome was the only parameter that affected the cost effectiveness of dual-chamber pacing: assumptions of 0% severe pacemaker syndrome with single-chamber pacing increased the ICER of dual-chamber pacing to £10,444 per QALY. |
| 4.2.4 | Guidant submitted a Markov model of the costs and outcomes of dual-chamber pacing compared with single-chamber ventricular pacing in a population of patients with sick sinus syndrome and atrioventricular block over a 10-year time horizon. Dual-chamber pacing was associated with an incremental cost of £742 and incremental benefits of 0.399 QALYs over 10 years compared with single-chamber ventricular pacing, to give an ICER of approximately £1800 per QALY. Sensitivity analysis of the cost effectiveness of dual-chamber pacing in younger patients (50 years of age, over a 30-year time horizon) showed the dominance of dual-chamber pacing, which was less costly and generated more QALYs than did single-chamber pacing. |
| 4.2.5 | St Jude Medical submitted a model that compared the costs and outcomes of dual-chamber with single-chamber pacing in patients with atrioventricular block and sick sinus syndrome, or sick sinus syndrome alone over a 7.5-year time horizon. Dual-chamber pacing was associated with an incremental cost of £438, which is offset by a reduction in the cost of adverse events (severe pacemaker syndrome, stroke, heart failure and atrial fibrillation) demonstrating a cost saving of £182 for a mixed population of patients with sick sinus syndrome and atrioventricular block (or the avoidance of 101 adverse events), or cost saving of £265 for a population of patients with sick sinus syndrome alone (or the avoidance of 56 events). Sensitivity analysis demonstrated that the incidence of pacemaker syndrome had a major effect on the cost effectiveness of dual-chamber pacing. |
| 4.2.6 | The Assessment Group developed separate models that compared the cost and outcomes of dual-chamber compared with single-chamber pacing in populations of patients with sick sinus syndrome and atrioventricular block over a 10-year time horizon. The atrioventricular block model compared dual-chamber with single-chamber ventricular pacing, and the sick sinus syndrome model compared dual-chamber with single-chamber atrial pacing. The models were similar in structure. A hypothetical cohort of 2000 75-year-old patients entered each model immediately before pacemaker implantation, during which they could develop perioperative complications. After successful pacemaker implantation, patients progressed through the model in one -monthly cycles between the following health states: postoperative complications; well with pacemaker; health states associated with complications (atrial fibrillation, heart failure, stroke), which could occur in any arm of the model; mild and severe pacemaker syndrome (which only occurred in the single-chamber ventricular pacing arm); generator expiry; upgrade to a dual-chamber pacemaker; or death. Patients progressed to death from any health state, although the transition probability was specific to the previous health state (for example, risk of death from stroke) where possible. |
| 4.2.7 | Baseline estimates of the effectiveness of single-chamber pacing were based on trials identified in the systematic review. The relative effectiveness of dual -chamber pacing was incorporated into the model by applying the relative risk estimates from the meta-analysis or from individual trials to the baseline parameters. |
| 4.2.8 | Data on the costs of pacemaker hardware were based on the aggregate market prices of pacemakers in the draft report of the UKPACE cost-utility analysis. The costs of pacemakers varied depending on the type of device: VVI (£690), VVIR (£1099), DDD (£1365) and DDDR (£2017); atrial leads were £175 and ventricular leads £172. The proportion of rate-responsive single- and dual-chamber pacemakers used in the model was based on the proportion of rate-responsive and non-rate-responsive devices reported in the clinical trials. In the ventricular pacing arm of the model 24% of devices were VVI and 76% of devices were VVIR, and in the dual chamber arm there was an equal proportion of DDD and DDDR pacemakers. The cost of the implantation procedure was estimated using cost data from the Resource Cost Initiative and incorporated differences in the costs of dual- and single-chamber devices. |
| 4.2.9 | Utility estimates were based on the PASE trial (in which a time trade-off method elicited patient preferences for different health states) or reports of studies in the Harvard Catalogue of Preference Scores. Utility for the cycle of pacemaker implantation was 0.76, and the utility of ?well with pacemaker' was 0.925. All complications (including pacemaker upgrade or replacement) were associated with a utility decrement of 0.01 based on clinicians' estimates. |
| 4.2.10 | The Assessment Group model contained a number of assumptions related to the incidence of complications with different pacing modes. Pacemaker syndrome (4% severe pacemaker syndrome and 22% mild pacemaker syndrome) only occurred in the single-chamber ventricular pacing arm; patients with severe pacemaker syndrome were upgraded to a dual-chamber pacemaker, and mild pacemaker syndrome was chronic. The progression of atrioventricular block in sick sinus syndrome was modelled only in the single-chamber atrial pacing arm; these patients were upgraded to a dual-chamber device. When atrial fibrillation occurred with dual-chamber pacing, devices were reprogrammed to single-chamber ventricular pacing and patients assumed the same risk of atrial fibrillation, stroke and heart failure as with single-chamber ventricular pacing. |
| 4.2.11 | The base-case scenario of the atrioventricular block model was based on the UKPACE survey of the market price of pacemakers, and the assumption that mild pacemaker syndrome did not resolve (these patients had a utility of 0.80 for the remainder of their lifetime). Dual-chamber pacing was associated with an increased cost of £700 and an additional 0.082 QALYs at 5 years, giving an ICER of £8500 per QALY. The ICER of dual-chamber pacing decreases as benefits are accrued over a 10-year time horizon giving an ICER of £5500 per QALY. |
| 4.2.12 | One-way sensitivity analysis demonstrated that the variations in implantation cost, background mortality rate, perioperative complication rate, atrial fibrillation, heart failure, stroke and generator replacement had little effect on the cost effectiveness of dual-chamber pacing in atrioventricular block. However, the cost effectiveness of dual-chamber pacing is sensitive to variations in list prices between dual- and single-chamber pacemakers and assumptions about the incidence and resolution of mild pacemaker syndrome. A sensitivity analysis that evaluated the cost effectiveness of dual-chamber pacing based on the market price of devices supplied by the ABHI (section 3.2) resulted in ICERs of £7000 (5-year time horizon) and £4600 (10-year time horizon). Another sensitivity analysis varied the price of pacemakers to approximate a minimum (dual-chamber £5200, single-chamber atrial and ventricular pacemaker £4600), average (dual-chamber £6500, single -chamber atrial and ventricular pacemaker £4900) and maximum (dual -chamber £8400 and single-chamber atrial and ventricular pacemaker £5300) list price of pacemakers. At the minimum and average assumed list prices of pacemakers, dual-chamber pacing is associated with an ICER of below £16,000 per QALY at 5 years. However, the ICER rose to £34,000 per QALY when the assumed maximum cost of devices was used. Sensitivity analysis that assumed that 50% of cases of mild pacemaker syndrome resolve into a controlled state (compared with 0% in the base case) increased the ICER to £36,000 per QALY at 5 years and £18,000 per QALY at 10 years. |
| 4.2.13 | The results of the model of dual-chamber pacing in sick sinus syndrome demonstrated that dual-chamber pacing is dominated by single-chamber atrial pacing, because atrial pacing generates more QALYs and is less costly than dual-chamber pacing. Sensitivity analysis showed that single-chamber atrial pacing dominates dual-chamber pacing in all scenarios. |
| 4.3 | Consideration of the evidence |
| 4.3.1 | The Committee reviewed the evidence available on the clinical and cost effectiveness of dual-chamber pacing, having considered evidence on the nature of the condition and the value placed on the benefits of dual-chamber pacing by users, those who represent them, and clinical experts. The discussions were also informed by consideration of the clinical appropriateness of pacing for different underlying causes of bradycardia. It was also mindful of the need to take account of the effective use of NHS resources. |
| 4.3.2 | The Committee considered the evidence that dual-chamber pacemakers were used less often in patients older than 75 years. Experts commented that the underlying reason for this could be that clinicians consider that patients who are more active are more likely to derive the most benefit from dual-chamber pacing. Also, younger patients have a longer life expectancy and therefore are more likely to be affected in the longer-term by complications associated with single-chamber pacing. However, the Committee were aware that an improved response to increased activity may also be enhanced by rate-responsive single-chamber pacemaker devices. |
| 4.3.3 | The Committee considered evidence on the clinical effectiveness of dual-chamber pacing compared with single-chamber ventricular pacing and was aware of the difficulty in extrapolating evidence from the large RCTs in mixed populations (and pooled data on the effectiveness across all sick sinus syndrome and atrioventricular block populations) to patients presenting with either sick sinus syndrome or atrioventricular block. The Committee heard evidence from experts that some of the large RCTs compared pacing modes that were not recommended by the BPEG guidelines (for example single-chamber ventricular pacing for sick sinus syndrome without atrioventricular block), and that the evidence based on the trial populations, which had mean ages of 73 to 80 years, may not be applicable to younger patients. The Committee also heard from the experts that there was considerable overlap between sick sinus syndrome and atrioventricular block, in that up to 30% of people with sick sinus syndrome also have atrioventricular block, and that the options for appropriate pacing modes need to take this into account. |
| 4.3.4 | The Committee considered the benefits of dual-chamber pacing compared with single-chamber ventricular pacing, particularly reductions in the incidence of atrial fibrillation and pacemaker syndrome , and improvements in exercise tolerance, alongside evidence on the higher incidence of device-related perioperative and postoperative complications with dual-chamber compared with single-chamber pacing. The Committee also heard evidence that subsequent device replacements (for example, because of generator expiry or upgrade from single-chamber to dual-chamber pacing devices) are associated with a higher incidence of complications than are primary implants. Experts advised that dual-chamber devices may have a shorter life expectancy and need to be replaced up to one year earlier than do single-chamber pacemakers, although this also depends on the degree of pacemaker dependency and on the specific programming features of the device. |
| 4.3.5 | The Committee considered the evidence on the incidence of pacemaker syndrome in single-chamber ventricular pacing. The literature estimates varied from 4 to 26% and the Committee was aware that this could be partly attributed to difficulties in the diagnosis of pacemaker syndrome because there is overlap in the symptoms of pacemaker syndrome with many symptoms typical of cardiac disease, and with symptoms arising from co -morbidities, particularly in the elderly. Experts advised that severe pacemaker syndrome arises in about 4% of patients, and that the incidence of mild pacemaker syndrome is likely to be less than 15%, although a precise estimate could not be given. The Committee heard from experts that patients with mild pacemaker syndrome often adapt over time to the condition. |
| 4.3.6 | The Committee considered the equivocal evidence on the quality of life with dual-chamber pacing compared with single-chamber ventricular pacing reported in the clinical trials. Clinical and patient experts testified to the dramatic improvement in quality of life with pacing (both dual- and single -chamber) compared with quality of life before pacing. The Committee heard from experts that dual-chamber pacing was favoured in disease-specific quality of life questionnaires and crossover studies that elicited patient preference. |
| 4.3.7 | The Committee reviewed all the data and economic models on the cost effectiveness of dual-chamber pacing compared with single-chamber ventricular pacing in atrioventricular block. |
| 4.3.8 | The Committee considered the Assessment Group model, particularly the incidence of and utilities associated with mild and severe pacemaker syndrome, which are key drivers of cost effectiveness. The Committee heard from experts that the 4% incidence of severe pacemaker syndrome was appropriate, but the model may overestimate the incidence of mild pacemaker syndrome, and pacemaker syndrome-like symptoms may also occur with dual-chamber pacing, albeit infrequently. The Committee also considered that the disutility associated with mild pacemaker syndrome (0.80 compared with 0.62 for severe pacemaker syndrome, and 0.925 for ?well with pacemaker') may have been overestimated in the Assessment Group model. The Committee also considered the cost effectiveness of dual-chamber pacing compared with single-chamber ventricular pacing based on the market price of devices supplied by the ABHI, and the likely list price of devices. The Committee considered that while the ICER for dual-chamber pacing over single-chamber ventricular pacing (based on the list price of devices) in atrioventricular block was likely to be significantly higher than identified in the Assessment Group model's central estimates, dual-chamber pacing was still likely to be a cost-effective alternative to single-chamber ventricular pacing. |
| 4.3.9 | The Committee considered the evidence base on the effectiveness of dual-chamber pacing compared with single-chamber atrial pacing for sick sinus syndrome. The Committee heard from experts that up to 30% of patients with sick sinus syndrome do not have any evidence of atrioventricular block (after provocation testing) and therefore may be suitable for single-chamber atrial pacing. Although single-chamber atrial pacing is currently the mode recommended by the BPEG for sick sinus syndrome without atrioventricular block, experts commented on low adherence to BPEG guidance. Experts advised that single-chamber atrial pacing is superior to single-chamber ventricular pacing for people with sick sinus syndrome without any evidence of atrioventricular block on provocation testing at the time of pacemaker implant, because of the incidence of pacemaker syndrome associated with ventricular pacing. |
| 4.3.10 | The Committee considered that single-chamber atrial pacing was likely to be more clinically effective than dual-chamber pacing in the treatment of sick sinus syndrome with normal AV conduction as the evidence reviewed indicated that it was associated with lower rate of atrial fibrillation and improved exercise tolerance. However, the Committee was aware that some people who receive single-chamber atrial pacing for sick sinus syndrome may subsequently go on to develop atrioventricular block and would therefore require an upgrade to a dual-chamber pacemaker. The Committee noted that the late development of atrioventricular block was uncertain and, although its occurrence was difficult to predict, there were certain identifiable risk factors. Accordingly, a thorough evaluation should be conducted at the time of initial pacemaker insertion. The Committee heard from experts that, when individual suitability for single-chamber atrial pacing is appropriately assessed, the incidence of subsequent development of atrioventricular block in patients with sick sinus syndrome is likely to be as low as 1 or 2% per annum. |
| 4.3.11 | The Committee reviewed data on the cost effectiveness of dual-chamber pacing compared with single-chamber atrial pacing in sick sinus syndrome without atrioventricular block. Single-chamber atrial pacing dominated dual-chamber pacing as it is more effective and less costly. The Committee concluded that single-chamber atrial pacing was the most clinically appropriate pacing mode for sick sinus syndrome without atrioventricular block in people who had been fully assessed for the presence of, and risk factors related to, the development of atrioventricular block. |
| 4.3.12 | The Committee was aware that dual-chamber pacing is not clinically appropriate for the treatment of atrioventricular block with chronic atrial fibrillation as the atrium will not respond to atrial pacing, and sensing of the atrial chamber is not appropriate in these circumstances. |
| 4.3.13 | Experts advised that rate responsiveness in both dual- and single-chamber pacing was preferable to using non-rate-modulating devices. This was usually considered to be particularly important for patients with sinus node dysfunction as the atrial pacing rate of these patients does not increase appropriately in response to physiological and metabolic requirements. However, the evidence did not separately consider the effectiveness and cost effectiveness of rate responsiveness, and that devices with this feature are more costly than the non-rate-responsive devices. The Committee considered that decisions about whether to implant a rate-responsive or a non -rate -responsive device should be made using clinical judgement on an individual patient basis. |
| 4.3.14 | In summary, the Committee concluded that, where clinically appropriate (for people who have sick sinus syndrome with atrioventricular block, and for those with atrioventricular block without chronic atrial fibrillation ), dual-chamber pacing is an acceptable alternative to single-chamber ventricular pacing. Single-chamber atrial pacing is the clinically appropriate pacing mode for people with sick sinus syndrome without atrioventricular block (single-chamber ventricular pacing is contraindicated in this group and dual-chamber pacing is associated with an increased incidence of atrial fibrillation). Single-chamber ventricular pacing is the clinically appropriate pacing mode for people with atrioventricular block with chronic atrial fibrillation (dual-chamber pacing is contraindicated in this group). |
| 5 | Proposed recommendations for further research |
| 5.1 | The publication of the UKPACE trial will provide additional data on quality of life with dual-chamber pacemakers compared with single-chamber ventricular pacemakers |
| 5.2 | The ongoing DANPACE trial will provide additional information on the effectiveness of dual-chamber pacing compared with single-chamber atrial pacing in patients with sick sinus syndrome without atrioventricular block |
| 5.3 | The Institute recommends that further studies evaluate the incidence of mild pacemaker syndrome, and utilities associated with health states of mild and severe pacemaker syndrome |
| 5.4 | Further research into the predictors for the development of atrioventricular block in sick sinus syndrome to determine people for whom single-chamber atrial pacing is appropriate is also recommended |
| 5.5 | Further studies should evaluate the effectiveness of dual- and single-chamber pacing at follow up beyond 5 years (where possible up to 20 years) for outcomes of mortality, stroke, heart failure, atrial fibrillation and pacemaker syndrome |
| 6 | Preliminary views on the resource impact for the NHS |
| This section outlines the Appraisal Committee's preliminary assessment concerning the likely impact on NHS resources if the recommendations in Section 1 were to be implemented. When guidance is issued, this section is intended to assist NHS planners and managers in its implementation. Therefore the Institute particularly welcomes comments and information from those who would be involved in the implementation of the guidance so that this section can be made as helpful and robust as possible | |
| 6.1 | Approximately 25,000 pacemakers are implanted every year in the UK; three quarters of these are first implants, and one quarter are replacements |
| 6.2 | The current hardware cost of pacemaker implantation based on the market cost of pacemakers and leads (see Section 4.2.8) and the proportion of pacemaker types implanted is approximately £43 million per year |
| 6.3 | The anticipated additional cost of implementing this guidance, based on 90% uptake of dual-chamber pacemakers (clinicians advised that approximately 10% of patients have chronic AF and would not be eligible for a dual chamber pacemaker), is approximately £10 million per year. This does not take into consideration potential differences in the staff and theatre costs between procedures for implanting dual- and single-chamber pacemakers. These estimates are based on the market price of devices, which may represent a substantial discount on the list price of pacemakers. |
| 6.4 | As a result of this guidance, patients with sick sinus syndrome who have no evidence of atrioventricular block after provocation testing should receive a single-chamber atrial pacemaker instead of a single-chamber ventricular pacemaker. This change will not have a significant cost impact because of the similar price of single-chamber pacemakers (atrial and ventricular) and leads. Although no data are available, it is likely that some patients may be inappropriately receiving a dual-chamber pacemaker for this indication. As these patients should now receive a single-chamber atrial pacemaker, this will lead to cost savings |
| 6.5 | The incremental cost of implanting dual-chamber pacemakers in patients who currently receive a single-chamber ventricular pacemaker will be partially offset by the cost of upgrading to a dual-chamber pacemaker in patients who develop severe pacemaker syndrome. |
| 7 | Proposals for implementation and audit |
| This section presents proposals for implementation and audit based on the preliminary recommendations for guidance in Section 1. | |
| 7.1 | Clinicians who care for people who have symptomatic bradycardia associated with sick sinus syndrome and/or atrioventricular block should review their current practice and policies to take account of the guidance set out in Section 1. |
| 7.2 | Local guidelines, protocols or care pathways that refer to the care of people with symptomatic bradycardia associated with sick sinus syndrome and/or atrioventricular block should incorporate the guidance. |
| 7.3 | To measure compliance locally with the guidance, the following criteria could be used. Further details on suggestions for audit are presented in Appendix C. |
| 7.3.1 |
Dual-chamber pacing is used for the management of symptomatic bradycardia associated with sick sinus syndrome, atrioventricular block, or a combination of sick sinus syndrome and atrioventricular block except in the following circumstances.
|
| 8 | Related guidance |
| 8.1 |
The Institute has two ongoing related Technology Appraisals.
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| 8.2 |
The Institute has one related ongoing Clinical Guideline.
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| 9 | Proposed date for review of guidance |
| 9.1 | The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review. |
| 9.2 | It is proposed that the guidance on this technology is reviewed January 2007 |
| David Barnett |
| Chair, Appraisal Committee |
| July 2004 |
| Appendix A. Appraisal Committee members |
| NOTE The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets three times a month except in December, when there are no meetings. The Committee membership is split into three branches, with the chair, vice-chair and a number of other members between them attending meetings of all branches. Each branch considers its own list of technologies and ongoing topics are not moved between the branches. |
| Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal. |
| The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website. |
| Dr Jane Adam Radiologist, St George's Hospital, London |
| Professor Ron Akehurst Dean of School of Health and Related Research, University of Sheffield |
| Dr Sunil Angris General Practitioner, Waterhouses Medical Practice, Staffordshire |
| Professor David Barnett (Chair) Professor of Clinical Pharmacology, University of Leicester |
| Professor John Cairns Professor of Health Economics, Health Economics Research Unit, University of Aberdeen |
| Professor David Chadwick Professor of Neurology, Department of Neurological Science, Walton Centre for Neurology & Neurosurgery, Liverpool |
| Dr Paul Ewings Statistician, Taunton & Somerset NHS Trust, Taunton |
| Dr Trevor Gibbs Industry Representative, Head, Global Clinical Safety & Pharmacovigilance, GlaxoSmithKline, Greenford |
| Mr Sanjay Gupta Stroke Services Manager, Basildon & Thurrock University Hospitals NHS Trust |
| Dr Peter Jackson Clinical Pharmacologist, Molecular & Clinical Pharmacology, University of Sheffield |
| Dr Mike Laker Medical Director, Newcastle Hospitals NHS Trust, Royal Victoria Infirmary, Newcastle-Upon-Tyne |
| Mr Terence Lewis Mental Health Consultant, National Institute for Mental Health in England, Solihull, West Midlands |
| Professor Richard Lilford Professor of Clinical Epidemiology, Department of Public Health and Epidemiology, University of Birmingham |
| Professor John Lumley Honorary Consultant, The Ernest Cooke Clinic Microvascular Unit, Great Ormond Street, Bart's and the Royal London NHS Trust, Barbican, London |
| Dr Simon Mitchell Consultant Neonatal Paediatrician, St Mary's Hospital, Manchester |
| Dr Stephen Saltissi Consultant Cardiologist, Royal Liverpool University Hospital |
| Dr Lindsay Smith General Practitioner, Westlake Surgery, Somerset |
| Mr Mike Spencer General Manager, Clinical Support Services, Cardiff and Vale NHS Trust |
| Professor Mary Watkins Professor of Nursing, University of Plymouth |
| Dr Norman Waugh Department of Public Health, University of Aberdeen |
| Mrs Miranda Wheatley-Price Lay Representative, Director of Service Development, Colon Cancer Concern, London |
| NICE Project Team |
| Each appraisal of a technology is assigned to a Health Technology Analyst and a Technology Appraisal Project Manager within the Institute. |
| Eleanor Donegan Technical Lead, NICE project team |
| Nina Pinwill Project Manager, NICE project team |
| Appendix B. Sources of evidence considered by the Committee | |
| A | The assessment report for this appraisal was prepared by Peninsula Technology Assessment Group. |
| Castelnuova E, Stein K, Pitt M et al. (May 2004) The effectiveness and cost effectiveness of dual chamber pacemakers compared to single chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome; systematic review and economic evaluation | |
| B | The following organisations accepted the invitation to participate in this appraisal. They were invited to make submissions and comment on the draft scope and assessment report. They are also invited to comment on the ACD and consultee organisations are provided with the opportunity to appeal against the FAD. |
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I Manufacturer/sponsors:
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II Professional/specialist and patient/carer groups:
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III Commentator organisations (without the right of appeal):
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| C |
The following individuals were selected from clinical expert and patient advocate nominations from the professional/specialist and patient/carer groups. They participated in the Appraisal Committee discussions and provided evidence to inform the Appraisal Committee's deliberations. They gave their expert personal view on dual-chamber pacing by attending the initial Committee discussion and/or providing written evidence to the Committee. They are invited to comment on the ACD.
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| Appendix C. Detail on criteria for audit of the use of dual-chamber pacemakers for symptomatic bradycardia due to sick sinus syndrome and/or atrioventricular block | |||
| Possible objectives for an audit | |||
| An audit could be carried out to ensure that dual-chamber pacing is used appropriately for the management of symptomatic bradycardia due to sick sinus syndrome and/or atrioventricular block. | |||
| Possible patients to be included in the audit | |||
| An audit could be carried out on people with symptomatic bradycardia associated with sick sinus syndrome, atrioventricular block, or a combination of sick sinus syndrome and atrioventricular block, who are seen in a reasonable period for audit, for example, 3 or 6 months. People with more complex pacing indications involving bradycardia for indications such as after cardiac transplantation, the occurrence of intermittent tachycardias or pacing specifically for advanced heart failure should be excluded from this audit. | |||
| Measures that could be used as a basis for an audit | |||
| The measure that could be used in an audit of the management of symptomatic bradycardia to ensure that dual-chamber pacing is considered appropriately is as follows. | |||
| Criterion | Standard | Exception | Definition of Terms |
|
1. Dual-chamber pacing is used for the management of symptomatic bradycardia associated with any of the following: a. sick sinus syndrome (SSS) b. atrioventricular block (AVB) c. a combination of SSS and AVB |
100% of people with symptomatic bradycardia associated with SSS, AVB or a combination of SSS and AVB | A. The patient has SSS with no evidence of AVB and single-chamber atrial pacing is used or B. The patient has AVB with chronic atrial fibrillation and single-chamber ventricular pacing is used |
Sick sinus syndrome is also known as sinus node dysfunction. See Appendices D and E for pacemaker nomenclature and pacing modes. |
| Calculation of compliance with the measure | ||
| Compliance (%) with each measure described in the table above is calculated as follows. | ||
| Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed | ||
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X 100 | |
| Number of patients to whom the measure applies | ||
| Number of patients whose care is consistent with the criterion plus number of patients who meet any exception listed | ||
| Clinicians should review the findings of measurement, identify whether practice can be improved, agree on a plan to achieve any desired improvement and repeat the measurement of actual practice to confirm that the desired improvement is being achieved. | ||
| Appendix D. Pacemaker nomenclature | |
| In 1987 the North American Society of Pacing and Electrophysiology (NASPE) and the British Pacing and Electrophysiology Group (BPEG) set up the NBG (NASPE/BPEG Generic) code to describe different pacing modes. To incorporate new technologies such as dual-chamber pacing, this code was updated in 2002. | |
| The first letter of the code signifies the chamber being paced: O = none A = atrium V = ventricle D = dual (A + V) (Manufacturers' designation only: S = single [A or V]) |
|
| The second letter signifies the chamber being sensed: O = none A = atrium V = ventricle D = dual (A + V) (Manufacturers' designation only: S = single [A or V]) |
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| The third letter signifies the response to sensing: O = none I = inhibited T = triggered D = dual (T + I) |
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| The fourth letter signifies rate modulation: O = none R = rate modulation |
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| The fifth letter signifies multisite pacing: O = none A = atrium V = ventricle D = dual (A + V) |
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| For example, 'DDD' indicates dual-chamber pacing with no rate modulation or multisite pacing. 'AAI' indicates atrial pacing inhibited by sensed spontaneous atrial depolarisations; no rate modulation or multisite pacing. | |
| Appendix E. BPEG guidelines on pacing modes |
| Indication for pacing | Type of pacemaker recommended | |
| Sick sinus syndrome | Without atrioventricular block | Single-chamber atrial; AAI, AAIR |
| With atrioventricular block | Dual-chamber; DDDR, DDIR, DDD, DDI | |
| Atrioventricular block | Without chronic atrial fibrillation | Dual-chamber; DDD or VDD |
| With chronic atrial fibrillation | Single-chamber ventricular; VVIR or VVI | |
| Abbreviations: D; dual, V, ventricle; A, atrium; I, inhibited; R, rate responsive. |
This page was last updated: 30 March 2010