Europace Advance Access originally published online on May 11, 2006
Europace 2006 8(6):449-455; doi:10.1093/europace/eul042
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PACING/CRT
Modelling the health benefits and economic implications of implanting dual-chamber vs. single-chamber ventricular pacemakers in the UK
1 Caro Research Institute, 336 Baker Avenue, Concord, MA 01742, USA ; 2 Caro Research Institute, Eslov, Sweden; 3 Division of General Internal Medicine, Royal Victoria Hospital, McGill University, Montreal, Que., Canada
Manuscript submitted 15 July 2004. Accepted after revision 23 February 2006.
* Corresponding author. Tel: +1 978 371 1660; fax: +1 978 371 2445. E-mail address: jcaro{at}caroresearch.com
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Abstract |
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Aims To estimate the consequences of managing bradycardia due to sinoatrial node disease or atrioventricular block with dual-chamber vs. single-chamber ventricular pacemakers.
Methods and results A discrete-event simulation was conducted to predict outcomes over 5 years. Patients could develop post-operative complications, clinically relevant pacemaker syndrome leading to replacement of single-chamber with dual-chamber, atrial fibrillation (AF; which if chronic might require anticoagulants) or stroke. Survival, quality-adjusted life years (QALYs), complications, and associated direct medical costs were estimated (2003 British Pounds £). Identical patients were simulated after receiving a single-chamber device or a more expensive dual-chamber pacemaker. Probabilities of conditions were obtained from clinical trials. Benefits were discounted at 1.5% and costs at 6%. Post-operative complications increased from 6.4% with single-chamber to 7.7% with dual-chamber but AF decreased (22 vs. 18%) as did clinically relevant pacemaker symptoms (16.8 vs. 0%). Approximately £4300 were accrued per patient over 5 years. Additional health benefits with dual-chamber are achieved at a mean net cost of £43 per patient, leading to 0.09 QALY with a cost-effectiveness ratio of £477/QALY.
Conclusion Implanting the costlier device increases the cost of the initial operation; however, this is expected to be offset by a reduction in costs associated with re-operations and AF.
Key Words: Dual-chamber pacemaker, Costs, Cost-effectiveness, UK
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Introduction |
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Implantation of pacemakers has become an established approach to bradycardia due to sinoatrial node disease or atrioventricular block and this has become an increasingly common procedure. Over 18 000 patients in the UK and Ireland received their first pacemaker implant during 2002 and over two-thirds of these patients were elderly (over 70 years).1
Although at least a third of the systems were single-chamber, dual-chamber devices were more frequently selected. Atrial pacemakers account for only 1.1% of the total and are not considered in these analyses.2
Ventricular pacing increases the incidence of atrial fibrillation (AF) and in patients with sinus node dysfunction increases the risk of heart failure symptoms when compared with dual-chamber pacing.3–5 In addition, dual-chamber systems reduce the risk of patients developing pacemaker syndrome.3,6,7 So far, however, clinical trials have not found that these health benefits lead to a statistically significant increase in survival or reduction in the risk of a stroke.3,4 The prospective trials completed to date have established that the quality-of-life improves after a pacemaker is implanted, but have also found only a slight quality-of-life advantage from dual-chamber vs. single-chamber ventricular pacing.3,8 Among the patients who are intolerant of ventricular pacing, however, switching to dual-chamber pacing led to a significant improvement in their quality-of-life.9
Dual-chamber systems are more complex and also more costly than the single-chamber systems. The purpose of this study was to estimate the health and economic consequences in the UK of managing bradycardia due to sinoatrial node disease or atrioventricular block with a dual-chamber pacemaker vs. single-chamber ventricular pacing.
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Method |
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Model
This discrete-event simulation follows a patient's course after implantation of a pacemaker for treatment of bradycardia due to sinoatrial nodal disease or atrioventricular block. Two types of pacemaker devices were compared in these analyses: dual-chamber (DDD) and single-chamber ventricular pacing (VVI). Rate-modulated pacemaker systems (DDDR or VVIR) were also considered. Upon being assigned either dual- or single-chamber ventricular pacing, a specified proportion of patients receive the corresponding modulated device.
The model simulates individual patients. It considers the experience of a hypothetical population of patients, each implanted with either a single-chamber ventricular or a dual-chamber pacemaker system. During each simulation, characteristics are assigned to each of the 1000 individuals and then each patient is ‘twinned’ to ensure that all characteristics are identical in the two groups. One twin receives a dual-chamber device and the other a single-chamber ventricular device. The costs of the implantation are accrued at this time (including operation and pacemaker system), also taking into consideration whether a rate-modulated device is implanted.
During the simulation, each patient may develop post-operative complications, symptoms of pacemaker syndrome, a proportion of which are severe enough to lead to replacement of the single-chamber device with a dual-chamber device, AF (which may require anticoagulants), have a stroke, or die. The risks for developing each of the clinical outcomes are estimated for each individual according to the type of device implanted and other patient characteristics. The published risk profile for each device was used to derive the hazards for each of the outcomes modelled. These hazards are used in the model to compute the times at which each of the various events will occur in that patient by sampling the corresponding distribution of failure times. It is assumed that these distributions are independent, i.e. that the occurrence of one event does not directly influence the risks of the others.
Three times are initially calculated: detection of AF, occurrence of an implantation-related complication, and incidence of pacemaker syndrome. Life expectancy is also estimated and assumed to be the same regardless of the device. The simulation compares the times of the three main events and of death, selecting the next one and processing that event at the appropriate time. Any times that exceed the time horizon (5 years) or the time of death indicate that that particular event will not occur during the simulation.
If AF occurs, the simulation considers whether anticoagulation is initiated. For these analyses, only patients with permanent AF were candidates for anticoagulation; paroxysmal and persistent episodes were not. Depending on anticoagulation and other patient characteristics, the risk of stroke is estimated and used to derive the time of stroke for the patient. This time then enters the comparison with whatever other event times remain to be considered. If pacemaker syndrome occurs, the simulation assesses whether symptoms are severe enough to require upgrading the single-chamber device to a dual-chamber device. If so, the patient is sent back to hospital for re-operation and those costs are accrued. Complication risks are re-assessed and the patient then re-enters the main module. When implantation-related complications occur, the model assigns a type of complication and whether a re-operation is required; and if this is needed, sends the patient back to hospital. There the same process takes place: accrual of appropriate costs and re-estimation of the complication risks and times. A weight is assigned to each patient's time as it accrues during the simulation depending on what has happened, the time since the implantation and the type of device. All events and resource-use incurred are attributed to the assigned device, regardless of whether the patient has a second operation at some point to replace the initial device.
When patients die or reach the end of the time horizon, they are removed from the simulation. At that point, the model stores the total time survived after the initial implant procedure, the quality-adjusted time, and the final costs. From these individual data, the mean results and variance are estimated for each cohort.
The simulation is carried out using ARENA®,10 a software package that facilitates discrete-event simulations. ARENA starts by initializing the system clock, creating individual patients, and assigning each one many attributes (e.g. age and gender). These are assigned using weighted random sampling of the input distributions set by the user; either discrete (e.g. gender) or continuous (e.g. normal distribution with a mean and standard deviation). By sampling the failure time distributions, the times at which the various events will occur are determined for each patient. These distributions are created within ARENA from the hazard functions developed for each outcome. ARENA then advances to the time of the next event and processes it.
Data sources
The characteristics assigned to each patient in the simulated cohort at the start were drawn from distributions (Table 1) primarily based on the characteristics of the population undergoing a first pacemaker implant in Canadian Trial of Physiological Pacing (CTOPP).11 The age distribution was based on published data on the UK population having a pacemaker implanted during 2002.1 The systolic blood pressure distribution was from data published from the Framingham Heart Study for patients with AF.12
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The model parameters and risk functions are mainly based on published data from two long-term randomized trials: CTOPP and Mode Selection Trial in Sinus-Node Dysfunction (MOST) (see Table 2). CTOPP was a prospective randomized trial of 2658 patients conducted at 32 Canadian centres.4
,8,11,13,14 Patients requiring a pacemaker for symptomatic bradycardia were randomized to receive either a physiological or ventricular pacemaker. Those assigned to receive a ventricular pacemaker received a VVI or VVIR, 74.6% received the rate modulated device. Most patients randomized to receive a physiological pacemaker had a dual-chamber device (DDD or DDDR) implanted, 5.2% an atrial pacemaker, 5.6% a ventricular device, and 0.9% no pacemaker. The trial was completed in July 1998 and the follow-up period was then extended to July 2001, for a mean follow-up time of 6.4 years. MOST was a prospective trial of 2010 patients undergoing DDDR pacemaker implantation at 91 US centres between September 1995 and October 1999 and follow-up data have been published for 3 years post-implantation.3,15 In MOST, patients were implanted with DDDR devices and randomized to have the pacemaker programmed to operate in either VVIR or DDDR mode.
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The risk of developing post-operative complications (atrial or ventricular lead displacement, infection, pneumothorax, other) for the dual-chamber cohort, the type, and associated probability of re-operation were estimated based on the information collected during MOST because in CTOPP only a portion of the group randomized to physiological pacing received this type of device. To remain consistent, the rate for single-chamber devices was derived by applying the hazard ratio (0.42) observed in CTOPP vs. physiological devices. The probability of experiencing an implantation-related complication during the first post-operative month was therefore 2.10% for single-chamber and 4.8% for dual-chamber. In the absence of long-term data on implantation-related complications for VVIR devices (these were not published from CTOPP), these rates were assumed to be the same for both devices after the first month, 0.51% for the second month, and 1.50% annual thereafter.
In CTOPP, AF (defined as an ECG-documented episode lasting more than 15 min) occurred in 6.6% of patients with VVIR and physiological pacing reduced this by 18%. Chronic AF occurred in 3.84% with VVIR and a 27% relative risk reduction was observed with physiological pacing. Among those developing AF, 36% were prescribed anticoagulants. On the basis of these results, dual-chamber pacing was assumed to reduce the risk of AF by 18%; 58.2% of AF becomes chronic (lasting at least 1 week) for the single-chamber and 52.8% with the dual-chamber device; and 65% of the patients with chronic AF are prescribed an anticoagulant. The risk of a stroke in patients developing AF was estimated using a risk equation developed as part of the Framingham Heart Study specifically for use in patients with AF.12 The predictors in the risk equation are: age, gender, systolic blood pressure, diabetes, and prior stroke or transient ischaemic attack (TIA). For the patients assigned to receive anticoagulation treatment, a relative risk reduction of 0.55%16 was applied to the risk of stroke.
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The incidence of pacemaker symptoms (dizziness or fainting) was estimated, based on CTOPP, at 38% for single-chamber systems.8
In MOST, 18% of patients with a device set to VVIR mode developed pacemaker symptoms that were severe enough to switch them to a dual-chamber mode.3 Therefore, we assumed 47% of those developing pacemaker syndrome would have benefited from a dual-chamber system. Based on MOST, 69% of those who switched were assumed to crossover within 3 months of the first implant and 73% within 6 months.3
The time of death for each patient was estimated from an equation derived from data published by CTOPP.14 The cumulative risk of death from all causes was extracted from Kaplan–Meier plots for each pacemaker type, the published risk data were pooled, and the survival probability over time was then derived. These probabilities fit a linear equation extremely well (r2=0.99). For this simulation, the time t of death (i.e. the life expectancy) was estimated by solving the resulting survival equation
S(t)=–0.0049t+0.9924
t=–(S(t)–0.9924)/0.0049
where S(t) is the probability of survival at time t expressed in months post-implant. The estimate of t is derived by replacing S(t) with a random number between 0 and 1. This correctly samples the distribution of failure times.
Quality-of-life weights were based on the data collected using the time trade-off approach during MOST.3 On the basis of the reported utility scores, patients typically had a score of 0.73 before the implant (optimal health is assigned a utility of 1) showed an improvement after implantation (single-chamber +0.05 and dual-chamber +0.08 at 12 months) and then declined. In the MOST analyses, if a patient crossed over from single-chamber to dual-chamber pacing, their health status at the time of the crossover was carried forward from the last visit before they crossed over. Over 48 months, the authors reported there was a small increase in the change from baseline for the DDDR vs. the VVIR mode group (repeated-measures ANOVA adjusted change +0.02, P=0.06). For the simulation, a score immediately post-implant was derived from fitting the reported data (single-chamber 0.783 and dual-chamber 0.807) and then the scores decline (single-chamber 0.003 and dual-chamber 0.004 per year).
Costs
These analyses considered the direct medical costs accrued to the National Health Service in the UK. The direct medical cost associated with the initial implantation and each subsequent clinical event was applied over time to estimate the total cost of care over 5 years. Costs were reported in 2003 British Pounds Sterling (£) and discounted at 6% per annum. Cost estimates were inflated, where necessary, using the appropriate consumer price index.17
The cost assigned to the initial implantation, or to the replacement of a pacemaker, includes the implantation procedure and pacemaker system. The procedure costs, and probability of being managed as day cases, for a pacemaker implant were obtained from the Department of Health, NHS reference costs: £1962 for outpatient, £3177 for elective inpatient, or £3217 for non-elective case.18 If a post-operative complication led to re-operation, a replacement/revision procedure cost was accrued (day case £1503, inpatient elective £2395, and non-elective £2785).18
The costs for the pacemaker system were allocated in the model taking into account the assigned type of device: DDD (£1260), DDDR (£1864), VVI (£673), or VVIR (£937) (Consortium of Pacemaker Manufacturers, personal communication). After assignment to either the dual-chamber or the single-chamber cohort, a proportion received a rate-adaptive device: DDDR (48%) or VVIR (65%) (Consortium of Pacemaker Manufacturers).
The annual cost of anticoagulation was estimated at £432 per patient. This comprised the annual cost of warfarin 5 mg per day (£0.06),19 six physicians' visits per year associated with monitoring,18 and laboratory tests (Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, UK, personal communication).
The initial cost of stroke was estimated at £2157 per patient. This estimate was a weighted cost derived from the information published by the Department of Health for this Healthcare Resource Group (HRG).18
Analyses
Survival, quality-adjusted life years (QALYs), re-operation, replacement of the VVIR pacemaker, anticoagulation or stroke, and the associated direct medical costs were estimated over 5 years. For the base case scenario, costs are discounted at 6% and QALYs at 1.5% per year,20 other discount rates were examined in sensitivity analyses, including the recently announced guideline of 3.5% for both.21 Sensitivity analyses were conducted on all other key model parameters, and uncertainty in the base case estimates was examined using 100 model replications.
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Results |
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Overall, 29.1% of the patients in each cohort died within 5 years of the implant. Post-operative complications increased from 6.4% with single-chamber to 7.7% with dual-chamber, but AF decreased (22 vs. 18%) (Table 3). The proportions of patients each cohort remaining event-free are summarized in Figure 1. The mean discounted cost over 5 years was about £4300 per patient in either cohort (Results are the mean of 100 replications. Table 4). On the basis of 100 replications, the additional health benefits from dual-chamber devices are achieved with net costs ranging from a saving of £107 to an incremental cost of £182, with a mean of £43 additional cost per patient. The dual-chamber pacemaker was predicted to increase the discounted QALY by a mean of 0.09 years. The mean cost-effectiveness ratio was £477 per discounted QALY, with 26% of the replications indicating dominance for the dual-chamber pacemaker.
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The results are sensitive to the proportion of patients with a VVI(R) who would have a replacement device inserted because of pacemaker syndrome (Figure 2). For example, if, in practice, only 5% of those experiencing clinically relevant pacemaker syndrome symptoms with a VVI(R) have a second operation to implant a different pacemaker, the total cost over 5 years is predicted to be 14% higher for the dual-chamber than the single-chamber (equivalent to a net cost of £527 per patient receiving an implant) or £3143 per case of clinically relevant pacemaker syndrome avoided.
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The results from varying other key parameters, one at a time, are provided in Table 5 and the results to be consistent over broad ranges. For example, the pacemaker system costs used in these analyses assumed about two-thirds of the single-chamber cohort would receive a VVI(R). Increasing this proportion to 95% leads to the mean result being a small saving from using the dual-chamber pacemaker. When the post-operative complication rates are assumed to be equivalent for the two pacemaker systems, small savings are again predicted.
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Apart from the univariate analyses that examined the impact of various factors one at a time, an additional analysis was carried out to address the effect of varying multiple parameters simultaneously. Such an analysis is already partially completed in the other sensitivity analyses because many of the input values are selected from a distribution. Thus, age, some of the costs, and so on are all already subject to variation, even in the base case comparisons. The quality-of-life weights, AF probabilities, and those relating to occurrence of pacemaker syndrome are entered as single values, however. In the full second-order multivariate analyses, these parameters were also allowed to vary from replication to replication by imposing distributions around them. One hundred replications were carried out for these analyses, each of 1000 patient pairs. In 29% of these replications, the use of dual-chamber pacemakers is economically dominant (reduces cost and increases QALY), and in an additional 31% it is highly attractive, with ratios falling below £1000/QALY. Indeed, none of the ratios exceed £10 000/QALY.
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Discussion |
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This study predicts that although implanting a dual-chamber instead of a single-chamber pacemaker will increase the initial implantation cost, the reduction in the risks of AF and of developing clinically relevant pacemaker syndrome translate into offsetting costs over the subsequent course. This simulation estimates that the health benefits from using dual-chamber pacemakers can be achieved on average at little or no additional cost over 5 years. Other economic evaluations have adopted various approaches to the model design and data sources, but also conclude that dual-chamber pacing is likely to be a cost-effective alternative to single-chamber ventricular.2
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Pacemaker syndrome is a common concern in patients with ventricular pacemakers. Symptoms that physicians felt were sufficient to warrant switching from single- to dual-chamber pacing afflicted about one in five patients in two trials.3,9 These symptoms generally arose within 6 months of the implantation and became chronic in nature. For patients implanted with a dual-chamber device programmed to operate in single-lead mode, this is a straightforward switch; but not so when having to recommend to an elderly patient that a second operation be performed to implant a replacement device.24 In routine practice, the replacement rates may well be lower than was assumed for our base case (18% over 5 years) because of the reluctance to re-operate. In CTOPP, the replacement rates were only about 5% over 5 years (approximately 1% per year).13 In 1996, Sutton and Bourgeois22 reviewed the literature and derived similar estimates of replacement rates for VVI (1.1% per year). When only 5% are switched from single- to dual-chamber over 5 years, the benefits are predicted to be achieved at an additional cost of £527 per patient—a level that might generally be accepted as cost-effective. The economic results are therefore somewhat dependent on the clinical assessments and recommendations of physicians regarding re-operation vs. the impact of living with symptoms from pacemaker syndrome. Remaining problems in standardizing diagnostic criteria and measurement of the severity make it difficult to assess precisely the impact of reducing the risk of these symptoms.
Data published from two long-term randomized trials, CTOPP and MOST, were used to develop the risk equations used in the simulation. A key assumption of this model is that these rates should also apply to the UK. The estimates based on CTOPP for long-term clinical outcomes, such as the development of AF, would also be expected to be applicable to the UK population. It also seemed reasonable to assume that the majority of those with chronic AF will be prescribed an anticoagulant, although this estimate was based on a Canadian trial. The costs of managing paroxysmal AF were not considered in these analyses.
For this simulation, the parameters pertaining to implant-related complications were estimated based on the information collected during MOST.15 MOST was a large trial (2010 patients) of DDDR pacemaker implantation; unlike other studies of post-implant complications, these data were collected from 91 US centres, and included details on both the acute complication rates and follow-up data for 3 years post-implant. In the Pacemaker Selection in the Elderly Trial (PASE), patients also received a DDDR and the complication rates were similar, 6.4%7 and in MOST 4.8%15 during the first month. In CTOPP for the physiological devices, higher rates were observed (9%) vs. the single-chamber (3%). As with many other surgical procedures, the perioperative complication rates are believed to be influenced by the experience of the operator.25,26 In any case, these rates had little impact in the sensitivity analyses.
The quality-of-life weights were obtained from MOST because they were measured using an appropriate technique in a relevant patient population.3 Relying on these published data was somewhat limiting. Only the mean change in utilities was reported over time, precluding assignment of a differential utility if, e.g. a patient has a stroke or experiences pacemaker syndrome. There is evidence from PASE, however, that switching to dual-chamber pacing among patients who are intolerant of ventricular pacing can lead to a significant improvement in their quality-of-life.9 These simulations assumed that mortality rates were the same for each cohort and so overall only small net differences in mean QALYs were predicted.
The largest component of the 5-year cost is the initial operation to implant the pacemaker and the second is the cost of the pacemaker system itself. The estimates for operations were a weighted cost derived from the information published by the Department of Health. The pacemaker system costs and the proportion that are rate-modulated devices reflect the current UK market. Costs associated with milder complications leading only to additional physician visits were not considered. For example, heart failure symptoms may be less frequent among the patients with dual-chamber systems, but this was not included.5 Routine follow-up costs were also not considered, and these were considered to be higher for dual-chamber rather than single-chamber pacemakers in the study of Sutton and Bourgeois.22 Some pacing systems have sophisticated features, e.g. allowing more data to be recorded, or have improved programming capabilities.27–29 Any potential impact of these types of features which may be valued by clinicians on the cost of managing these patients was not addressed in these analyses.
Discrete-event simulation is a well-established approach to modelling processes over time.30 Although it has been used relatively little in medicine,31 it was chosen because it permits the development of realistic models and avoids over-simplification of the management of patients, while remaining very transparent.32
Although the risk of mortality and stroke has not been proven to differ between the dual- and single-chamber systems, other tangible health benefits have been established for the former.3–7 The use of two leads rather than one for the treatment of bradycardia can be anticipated to reduce the risk of patients experiencing clinically relevant pacemaker syndrome and of developing AF. The majority of pacemakers are implanted when patients are over 70 years old, but about one of the five survive to develop clinically relevant pacemaker syndrome if ventricular pacing is chosen. Although the size of the economic effects are dependent on the rate of re-operation to switch from single-chamber devices, our analyses suggest that the additional health benefits from implanting a dual-chamber pacemaker are achievable at a cost that is generally considered cost-effective.
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The authors are employees of Caro Research Institute (MA, USA), a consultancy that has also received grants for other unrelated research from various pharmaceutical companies. This work was supported by a grant from a consortium comprising representatives of companies marketing these devices in the United Kingdom. The sponsors were expressly prohibited from exerting any control over the model design, inputs, or analyses or over this manuscript. Caro Research has also received grants for other research from Medtronic, the maker of products potentially affected by this work.
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References |
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[1] National Pacemaker Database Report Annual 2002. Central Cardiac Audit Database. http://www.ccad.org.uk/ccadweb.nsf..
[2] Peninsula Technology Assessment Group. 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. Assessment Report for public consultation.pdf. http://www.nice.org.uk/pdf/DCP. (27 May 2004).
[3] Lamas GA, Lee KL, Sweeney MO, et al. Mode selection trial in sinus-node dysfunction: ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002; 346: 1854–62.
[4] Kerr CR, Connolly SJ, Abdollah H, et al. Canadian trial of physiological pacing: effects of physiological pacing during long-term follow-up. Circulation 2004; 109: 357–62.
[5] Thackray SD, Witte KK, Nikitin NP, Clark AL, Kaye GC, Cleland JG. The prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in a typical regional pacemaker population. Eur Heart J 2003; 24: 1143–52.
[6] Dretzke J, Toff W, Lip G, Raftery J, Fry-Smith A, Taylor R. Dual chamber versus single chamber ventricular pacemakers for sick sinus syndrome and atrioventricular block. Cochrane Database Syst Rev 2004; 2: CD003710.
[7] Lamas GA, Orav EJ, Stambler BS, Ellenbogen KA, Sgarbossa EB, Huang SK, Marinchak RA, Estes NA III, Mitchell GF, Lieberman EH, Mangione CM, Goldman L. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators. N Engl J Med 1998; 338: 1097–104.
[8] Newman D, Lau C, Tang AS, et al. Effect of pacing mode on health-related quality of life in the Canadian Trial of Physiologic Pacing. Am Heart J 2003; 145: 430–7.[CrossRef][Web of Science][Medline]
[9] Ellenbogen KA, Stambler BS, Orav EJ, et al. Clinical characteristics of patients intolerant to VVIR pacing. Am J Cardiol 2000; 86: 59–63.[CrossRef][Web of Science][Medline]
[10] Kelton WD, Sadowski RP, Sadowski DA. Simulation with ARENA 2003; 3rd ed. Boston McGraw-Hill.
[11] Skanes AC, Krahn AD, Yee R, et al. Progression to chronic atrial fibrillation after pacing. The Canadian Trial of Physiologic Pacing. CTOPP Investigators. J Am Coll Cardiol 2001; 38: 167–72.
[12] Wang TJ, Massaro JM, Levy D, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. J Am Med Assoc 2003; 290: 1049–56.
[13] Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 2000; 342: 1385–91.
[14] Tang AS, Roberts RS, Kerr C, et al. Relationship between pacemaker dependency and the effect of pacing mode on cardiovascular outcomes. Circulation 2001; 103: 3081–5.
[15] Ellenbogen KA, Hellkamp AS, Wilkoff BL, et al. Complications arising after implantation of DDD pacemakers: the MOST experience. Am J Cardiol 2003; 92: 740–1.[CrossRef][Web of Science][Medline]
[16] Hart RG, Halperin JL, Pearce LA, et al. Lessons from the Stroke Prevention in Atrial Fibrillation Trials. Stroke Prevention in Atrial Fibrillation Investigators. Ann Intern Med 2003; 138: 831–8.
[17] http://www.statistics.gov.uk/STATBASE/tsdataset.asp?vlnk=7172&More=Y..
[18] http://www.doh.gov/nhsexe/refcosts/2002app1xlsDepartment of Health. NHS Reference Costs 2002. (17 October 2003).
[19] http://admin.safescript.com/drugcgic.cgi/START Coumadin 5 mg 2003.
[20] .National Institute for Clinical Excellence. Guidance for manufacturers and sponsors 2001; London National Institute for Clinical Excellence.
[21] .National Institute for Clinical Excellence. Guide to the methods of technology appraisal. London National Institute for Clinical Excellence pp. 2004.
[22] Sutton R and Bourgeois I. Cost benefit analysis of single and dual chamber pacing for sick sinus syndrome and atrioventricular block: an economic sensitivity analysis of the literature. Eur Heart J 1996; 17: 574–82.
[23] .National Institute of Clinical Excellence. Dual chamber pacemakers for symptomatic bradycardia due to sick sinus syndrome and/or atrioventricular block. 2005; Technology Appraisal 88, February.
[24] Newman D. Relationships between pacing mode and quality of life: evidence from randomized clinical trials. Card Electrophysiol Rev 2003; 7: 401–5.[CrossRef][Medline]
[25] Tobin K, Stewart J, Westveer D, Frumin H. Acute complications of permanent pacemaker implantation: their financial implication and relation to volume and operator experience. Am J Cardiol 2000; 85: 774–6.[CrossRef][Web of Science][Medline]
[26] Parsonnet V, Bernstein AD, Lindsay B. Pacemaker-implantation complication rates: an analysis of some contributing factors. J Am Coll Cardiol 1989; 13: 917–21.[Abstract]
[27] Plummer CJ and McComb JM. Detection of atrial fibrillation by permanent pacemakers: observations from the STOP AF Trial. Card Electrophysiol Rev 2003; 7: 333–40.[CrossRef][Medline]
[28] Glotzer TV, Hellkamp AS, Zimmerman J, et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the Mode Selection Trial (MOST). Circulation 2003; 107: 1614–9.
[29] Waktare JE and Malik M. Holter, loop recorder, and event counter capabilities of implanted devices. Pacing Clin Electrophysiol 1997; 20: 2658–69.[Medline]
[30] Law AM and Kelton WD. Simulation Modeling and Analysis 2000; Boston McGraw-Hill.
[31] Jun JB, Jacobson SH, Swisher JR. Application of discrete-event simulation in health care and clinics: a survey. J Oper Res Soc 1999; 50: 109–23.
[32] Caro JJ. Pharmacoeconomic analyses using discrete event simulation. Pharmacoeconomics 2005; 23: 323–32.[CrossRef][Web of Science][Medline]
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