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Circulation. 1996;93:489-496

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*Heart Attack
*Pacemakers and Implantable Defibrillators

(Circulation. 1996;93:489-496.)
© 1996 American Heart Association, Inc.

Articles

Cost-effectiveness of Implantable Defibrillator as First-Choice Therapy Versus Electrophysiologically Guided, Tiered Strategy in Postinfarct Sudden Death Survivors

A Randomized Study

Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994, and published in abstract form in Circulation (1994;90[pt 2]:I-654).

Eric F.D. Wever, MD; Richard N.W. Hauer, MD; Guus Schrijvers, PhD; Frans J.L. van Capelle, PhD; Jan G.P. Tijssen, PhD; Harry J.G.M. Crijns, MD; Ale Algra, MD; Hemanth Ramanna, MD; Patricia F.A. Bakker, MD; Etienne O. Robles de Medina, MD

From the Heart-Lung Institute (E.F.D.W., R.N.W.H., H.R., P.F.A.B., E.O.R. de M.), the Department of Health Sciences (G.S.), and the Clinical Epidemiology Unit (A.A.), University Hospital and University of Utrecht; the Department of Experimental Cardiology (F.J.L. van C.), and the Department of Epidemiology (J.G.P.T.), University Hospital and University of Amsterdam; the Thoraxcenter (H.J.G.M.C.), University Hospital and University of Groningen; and the Interuniversity Cardiology Institute of the Netherlands, Utrecht.

Correspondence to Eric F.D. Wever, MD, Department of Cardiology, Heart-Lung Institute, University Hospital Utrecht, 100 Heidelberglaan, PO Box 85500, 3508 GA Utrecht, Netherlands.


*    Abstract
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 *Abstract
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down arrowResults
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Background Rising costs of health care, partly as a result of costly therapeutic innovations, are of concern to both the medical profession and healthcare authorities. The implantable cardioverter-defibrillator (ICD) is still not remunerated by Dutch healthcare insurers. The aim of this study was to evaluate the cost-effectiveness of early implantation of the ICD in postinfarct sudden death survivors.

Methods and Results Sixty consecutive postinfarct survivors of cardiac arrest caused by ventricular tachycardia or fibrillation were randomly assigned either ICD as first choice (n=29) or a tiered therapy starting with antiarrhythmic drugs and guided by electrophysiological (EP) testing (n=31). Median follow-up was 729 days (range, 3 to 1675 days). Fifteen patients died, 4 in the early ICD group and 11 in the EP-guided strategy group (P=.07). For quantitative assessment, the cost-effectiveness ratio was calculated for both groups and expressed as median total costs per patient per day alive. Because effectiveness aspects other than mortality are not incorporated in this ratio, other factors related to quality of life were used as qualitative measures of cost-effectiveness. The cost-effectiveness ratios were $63 and $94 for the early ICD and EP-guided strategy groups, respectively, per patient per day alive. This amounts to a net cost-effectiveness of $11 315 per patient per year alive saved by early ICD implantation. Costs in the early ICD group were higher only during the first 3 months of follow-up, but as a result of the high proportion of therapy changes, including arrhythmia surgery and late ICD implantation, costs in the EP-guided strategy group became higher after that. Patients discharged with antiarrhythmic drugs as sole therapy had the lowest total costs. This subset, however, showed extremely high mortality, resulting in a poor cost-effectiveness ratio ($196 per day). Invasive therapies and hospitalization were the major contributors to costs. If quality-of-life measures are taken into account, the cost-effectiveness of early ICD implantation was even more favorable. Recurrent cardiac arrest and cardiac transplantation occurred in the EP-guided strategy group only, whereas exercise tolerance, total hospitalization duration, number of invasive procedures, and antiarrhythmic therapy changes were significantly in favor of early ICD implantation.

Conclusions In terms of cost-effectiveness, early ICD implantation is superior to the EP-guided therapeutic strategy in postinfarct sudden death survivors.


Key Words: death, sudden • cost-benefit analysis • defibrillation • electrophysiology • trials


*    Introduction
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 up arrowAbstract
 *Introduction
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down arrowDiscussion
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Antiarrhythmic drug therapy has long been considered the cornerstone in the management of patients with life-threatening ventricular tachyarrhythmias.1 2 3 4 5 However, recent reports suggest that the ICD may be superior to drug therapy in terms of both clinical effectiveness6 7 8 9 and cost-effectiveness.10 11 12 13 Because these studies were retrospective and did not directly compare similar patient groups, the ICD has remained a "last-resort" therapy in many clinical practices. In a recent randomized study of postinfarct sudden death survivors, however, we found higher effectiveness of ICD implantation as first-choice therapy compared with a tiered treatment strategy guided by EP testing (EP-guided strategy), including antiarrhythmic drugs as first choice and, when they fail, nonpharmacological treatment modalities.14 15 16

Uncertainties still remain regarding the cost-effectiveness of ICD therapy.17 18 Rising costs of health care, caused partly by costly therapeutic innovations, are of concern to both the medical profession and healthcare authorities. For this reason, the ICD currently is not reimbursed by the healthcare system in the Netherlands.19 Although ICDs are expensive, this high cost does not necessarily mean that ICD therapy is associated with higher overall expenditures compared with established therapeutic modalities. The EP-guided therapeutic strategy, starting with antiarrhythmic drugs, is in most cases very expensive.11 20 21 22 Antiarrhythmic drug treatment fails in a considerable proportion of patients.4 11 This means that many patients will eventually have nonpharmacological therapy after multiple drug trials and a lengthy hospitalization with multiple EP studies and other diagnostic procedures. In particular, ablative surgery with frequently prolonged postoperative intensive care and/or last-resort ICD implantation has a major effect on total costs. Another reason for high costs may be readmissions and, in the case of repeated resuscitations, potentially long-lasting neurological sequelae. In addition, the EP-guided strategy may have an unfavorable psychological impact on the patients and their relatives. Moreover, in subgroups of patients without an ICD, a high sudden death rate persists.

We performed a cost-effectiveness analysis of ICD implantation as first-choice therapy versus the tiered, EP-guided strategy, as practiced in many centers, in a randomized study design.


*    Methods
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 up arrowAbstract
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 *Methods
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Patients, Treatment Allocation, and Effectiveness Assessment
The study was approved by the Institutional Review Boards of our institutions and carried out in postinfarct survivors of out-of-hospital cardiac arrest caused by documented VT or VF. Patients were recruited at the University Hospitals of Utrecht and Groningen between April 1989 and April 1993. Details on inclusion and exclusion criteria and the predefined study protocol were described previously.16 19 All patients had baseline inducibility of ventricular tachyarrhythmia. The programmed electric stimulation protocol was described previously.23 Randomization was stratified according to the number of normokinetic segments by use of left ventricular cineangiography.16 19 24 25 Fig 1Down provides a flowchart of the study. After randomization, therapy was started as soon as possible. Patients allocated to the EP-guided strategy were consequently treated according to the lower branch of the flowchart (see Fig 1Down), with antiarrhythmic drug therapy always the first step. Patients who failed drug therapy were subjected to VT surgery only if they had mappable VT and were anticipated to have an acceptable perioperative risk. This was judged primarily from analysis of the systolic function of the noninfarcted part of the left ventricle.16 19 24 25 Patients were discharged when antiarrhythmic therapy was considered effective and safe. Effectiveness of an intended therapy was guided by both noninvasive tests (continuous telemetry, Holter monitoring, and exercise testing) and repeated programmed electric stimulation.16 23 All patients were meticulously followed, and the study ended on January 1, 1994.



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  		Figure 1. Flowchart of the study, including a summary of the EP-guided strategy. In the EP-guided strategy, antiarrhythmic drug therapy was always the first step.

The cost-effectiveness analysis reported in the present study is based on the comparative effectiveness of the two treatment strategies published previously.16 Total mortality in the two groups was compared by use of the hazard ratio, which may be interpreted as relative risk; the precision of hazard ratio estimates was described by means of 95% CIs obtained from the Cox proportional-hazards model. The ICD used for this study was the Ventak P (Cardiac Pacemakers Inc).

Cost-effectiveness Analysis
Total Costs
Starting on the day of randomization, total costs incurred during initial hospitalization, readmissions, and follow-up were analyzed. We kept an account of all medical costs per patient, ie, hospitalization; visits to outpatient clinics; all diagnostic investigations; and all therapeutic procedures, including drug treatment and domiciliary care. For all studied patients, calculation of costs of diagnostic and therapeutic procedures (including physicians' fees) was based on the lowest class scale rates of Dutch private healthcare insurance used by the billing department of the University Hospital Utrecht. Table 1Down shows the costs of hospitalization and diagnostic and therapeutic cardiac procedures at the University Hospital of Utrecht and the costs of devices according to January 1990 and December 1993 cost scenarios. The in-hospital charges per day varied from $313 in January 1990 to $497 in December 1993, with a median of $426 in January 1992, regardless of the type of ward (all costs are given in US dollars). A sensitivity analysis of cost estimates was performed according to these three different levels of hospitalization charges. We did not use a discount rate because the median follow-up was only 2 years. Medians of total costs per patient in both study groups were compared. In the EP-guided group, total costs per patient in the subgroups of patients who remained on antiarrhythmic drugs as sole therapy, had map-guided arrhythmia surgery, or underwent late ICD implantation also were calculated separately. The development of expenses in survivors was estimated by both absolute and median values of total costs at consecutive 1-, 3-, and 6-month intervals after randomization and for the entire study period.


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  		Table 1. Costs of Hospitalization, Diagnostic and Therapeutic Procedures, and Devices

Cost-effectiveness
For the assessment of the cost-effectiveness, we used total mortality as the only primary end point of effectiveness. Cost-effectiveness of each strategy was expressed as a cost-effectiveness ratio. This ratio was estimated in two ways. First, it was estimated as the median of total costs per patient per day alive. This ratio was calculated by dividing total costs for each patient by the number of days the patient was alive. Subsequently, the median of these ratios per strategy was assessed. In the same way, the cost-effectiveness ratio was determined for the subgroups of the EP-guided treatment arm. Second, cost-effectiveness ratios per strategy were calculated by dividing total costs in absolute values by the total number of patient days alive at consecutive 1-, 3-, and 6-month intervals after randomization.

Quality-of-Life Aspects
Because effectiveness aspects other than mortality are not expressed in the cost-effectiveness ratio, the following factors reflecting quality of life (secondary end points) were used for additional description: major nonfatal events (recurrent cardiac arrest and cardiac transplantation), functional NYHA class, exercise tolerance, left ventricular ejection fraction, duration of hospitalization (initial and readmissions), number of invasive procedures, and changes of antiarrhythmic therapy. NYHA class and exercise duration were compared at randomization and 3 and 12 months after discharge; left ventricular ejection fraction, at randomization and 3 months after discharge.16 Differences in quality-of-life variables were assessed with the Mann-Whitney U test, with values of P<=.05 considered significant.


*    Results
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
*Results
down arrowDiscussion
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Patients, Treatment Allocation, and Effectiveness Assessment
Sixty consecutive patients were included. Twenty-nine were allocated to early ICD implantation and 31 to the EP-guided strategy. The two groups showed no differences in baseline characteristics.16 The mean ejection fraction of the included patients was approximately 0.30. The mean number of antiarrhythmic drug trials used in the EP-guided arm was 2.2 (median, 2; range, 1 to 5).16 Of the 31 EP-guided strategy patients, 24 (77%) had a trial with a class III antiarrhythmic agent. More than two drug trials were used in 9 patients in whom drugs had to be discontinued owing to adverse effects. Inferred from persistent inducibility, drug therapy was considered a failure in 20 of 31 patients. Table 2Down shows additional follow-up results for both strategies and for subgroups of the EP-guided arm. Median follow-up duration for all patients was 729 days (mean, 802 days; range, 3 to 1675 days); for the early ICD group, 871 days (mean, 881 days; range, 8 to 1675 days); and for the EP-guided group, 676 days (mean, 728 days; range, 3 to 1537 days). Longer follow-up for the early ICD group compared with the EP-guided group was attributable to the higher survival rate in the former (see Table 2Down). No patient was lost to follow-up.


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  		Table 2. Median Total Costs Per Patient and Cost-effectiveness Ratios for Both Therapy Strategies and Subgroups of EP-Guided Strategy at End of Follow-up

By the end of the study, about one half of the EP-guided patients (52%) ended up with a late ICD. In this study population, no patient was considered a suitable candidate for catheter ablation, and only a minority (6 patients, 19%) of highly selected patients underwent VT surgery.

Fifteen patients died, 4 in the early ICD group and 11 in the EP-guided group (see Table 2Up). There was a strong trend toward better survival in the early ICD group, but the difference was not statistically significant (hazard ratio, 0.34; 95% CI, 0.11 to 1.08; P=.07). Of the 11 patients of the EP-guided arm treated with antiarrhythmic drugs as sole therapy, 7 died.16

Cost-effectiveness Analysis
Total Costs
Table 2Up shows medians of total costs per patient for both strategies with calculations according to the three levels of hospital charges. Median total costs were similar for both strategies ($47 000 versus $47 500, 1992 scenario). These amounts, however, were uncorrected for the difference in follow-up duration between the two strategy arms, which was shorter for the EP-guided group because of higher mortality (often at an early stage). To correct for these factors, the development of expenditure in survivors was assessed by use of median values of total costs per patient at consecutive monthly intervals. Fig 2Down shows that compared with the overall EP-guided group, median total costs per patient in the early ICD group were higher only during the first 3 months of follow-up; after that, the EP-guided strategy was more costly. The difference in cost development is due to the costs associated with therapy changes, including arrhythmia surgery and late ICD implantation in the EP-guided group within this early 3-month period and to longer hospitalization.16 Table 3Down shows absolute values of total costs at consecutive 1-, 3-, and 6-month intervals after randomization. Total costs per patient over the entire study period were less for the early ICD group compared with the EP-guided strategy ($56 067 versus $63 032 per patient according to the 1992 scenario).



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  		Figure 2. Plot showing the calculation of medians of total costs per patient at monthly intervals for survivors in each strategy arm to correct for the difference in follow-up duration between the early ICD group and the EP-guided strategy (median duration, 871 versus 676 days) and the higher mortality in the EP-guided group. Dips in the curves are due to deaths of patients with high costs.


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  		Table 3. Total Costs and Cost-effectiveness Ratios in Various Periods

In both strategy arms, there was some unavoidable delay of surgical therapy (map-guided surgery and ICD implantation) due to logistics. The median duration of (in-hospital) delay was 12 days (range, 4 to 47 days) in the early ICD group and 5 days (range, 0 to 16 days) in the EP-guided strategy arm.

Patients remaining on antiarrhythmic drugs as sole therapy had the lowest total costs ($23 500 per patient) but the highest mortality (7 patients). The ICD device, surgery (including ICD implantation), and hospitalization were the primary contributors to total costs per patient for both strategies, as shown in Fig 3Down.



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  		Figure 3. Bar graph showing total costs (1992 cost scenario) per patient in both therapeutic strategies (T) and costs for noninvasive procedures (NP); invasive procedures (IP, eg, catheterizations, EP studies); drugs including antiarrhythmic drugs (D); surgical procedures, including map-guided surgery and ICD implantation and costs of the ICD device (S); and hospitalization (H). All values are medians.

Cost-effectiveness
Table 2Up shows cost-effectiveness ratios based on median values for both strategies and for the subgroups of the EP-guided arm. The early ICD strategy was more cost-effective than the EP-guided strategy, regardless of whether it is calculated according to the 1990, 1992, or 1993 scenario. Although patients remaining on antiarrhythmic drugs as sole therapy had the lowest total costs, this subset of patients, because of the extremely high mortality early during follow-up, showed the worst cost-effectiveness ratio ($196 according to the 1992 scenario). Table 3Up shows an estimation of the cost-effectiveness ratios of both strategies based on absolute values (1992 scenario) at consecutive 1-, 3-, and 6-month intervals after randomization and for the entire study period. When calculated in this way, cost-effectiveness of the early ICD strategy also appears to be better than that of the EP-guided strategy ($64 versus $87 per day alive).

Quality-of-Life Aspects
When quality-of-life aspects also are taken into account, cost-effectiveness of early ICD implantation appears even more favorable. Recurrent cardiac arrest and cardiac transplantation occurred in the EP-guided group only, whereas better exercise tolerance, shorter total hospitalization duration, and fewer invasive procedures and antiarrhythmic therapy changes were all significantly in favor of early ICD implantation. In contrast, NYHA classification and left ventricular ejection fraction were not significantly different between the two groups.16

Pulse Generator Replacement
Replacement of pulse generators because of end-of-life situations in 6 ICD patients (4 in the early ICD group) and replacement of the whole ICD system because of infection in 1 patient from the EP-guided group did not affect the cost-effectiveness ratio substantially (see Table 3Up, months 19 to 22 and 23 to end). The cost-effectiveness ratios of the 4 early ICD patients who underwent pulse generator replacement were $44, $48, $63, and $120 for the entire study period. The poor cost-effectiveness ratio of the last patient was due to lengthy institutionalization for psychiatric illness. The cost-effectiveness ratios of the two patients from the EP-guided strategy group who underwent pulse generator replacement were $55 and $100; the ratio for the patient whose entire ICD system was replaced was $178. The last patient also was readmitted twice for noncardiac surgery.


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
*Discussion
down arrowReferences
 
This is the first randomized trial to estimate the cost-effectiveness of ICD implantation as first-choice therapy. Cost-effectiveness was compared with the tiered therapeutic strategy guided by EP testing for life-threatening ventricular tachyarrhythmia. In the present study, this comparison was made in patients at high risk for recurrent life-threatening events after surviving an episode of cardiac arrest caused by VT or VF associated with chronic-stage myocardial infarction.4 26

The results of this cost-effectiveness study clearly favor early ICD implantation in this patient category. The cost-effectiveness ratio based on median values was $63 and $94 per patient per day alive in the early ICD and EP-guided groups, respectively (1992 scenario, see Table 2Up). The difference would account for a net cost-effectiveness ratio of $11 300 (saved costs) per patient per life-year saved. The ICD device, surgery (including ICD implantation), and hospitalization were the major contributors to total costs in both strategies (see Fig 3Up).

Costs of diagnostic and therapeutic procedures did not change substantially during the study period, whereas charges for hospitalization differed (see Table 1Up). Therefore, we performed a sensitivity analysis to estimate the extremes of costs and cost-effectiveness ratios exclusively according to the three different scenarios of hospitalization charges: the 1990, the 1992, and the 1993 scenarios. However, this did not result in major shifts (see Table 2Up).

Anticipating a wide range in costs per day alive, we decided to use median values to compare both strategies. Nevertheless, when cost-effectiveness for both strategies was defined as total costs in absolute values divided by total number of patient days alive (see Table 3Up), findings were comparable, ie, better for the early ICD strategy.

Effectiveness measures other than life expectancy, such as quality-of-life aspects, were not used for quantitative determination of the cost-effectiveness ratio. When such measures are taken into account, cost-effectiveness of early ICD implantation appears even more favorable. Recurrent cardiac arrest occurred in the EP-guided group only, whereas exercise tolerance, total hospitalization duration, number of invasive procedures, and antiarrhythmic therapy changes were all significantly in favor of early ICD implantation. One patient in the EP-guided group ended up with cardiac transplantation.16 Because quality-of-life testing has not generally been routine in cost-effectiveness analyses,27 28 we did not adjust the cost-effectiveness ratios for quality of life. We arbitrarily decided not to include ICD discharges in quality-of-life aspects. As Jung et al,29 reported, the delivery of multiple (more than five) shocks in a relatively short period (<=12 months) may have a negative impact on quality of life in ICD patients. However, except for 5 (3 early and 2 late ICD) patients, this was absent in our study. In addition, the proportion of patients with shocks in the early ICD group (62%) was not different from that in the subgroup with late ICD implants in the EP-guided group (63%).16

Costs in the early ICD group were higher only during the first 3 months of follow-up (see Fig 2Up). Thereafter, the EP-guided strategy was more expensive. The difference in cost development was due to costs associated with therapy changes, including arrhythmia surgery and late ICD implantation, within the early 3-month period in the EP-guided group. This finding should be taken into account in the continuing discussion on mortality benefits of the ICD.18 30 31

In both strategy arms, there was some unavoidable delay of surgical therapy. If this delay could have been avoided, median total costs would have been lower for both strategies, $40 300 instead of $47 000 per patient for the early ICD group and $46 900 instead of $47 500 per patient for the EP-guided strategy group (see Table 2Up).

According to the 1992 scenario, the costs for early ICD implantation would be $23 000 (63x365) per patient per year of life saved. This is well within the range of costs of other accepted therapies, such as coronary artery bypass surgery ($7700 to $44 200), treatment of hypertension ($11 100 to $23 200), and nefrodialysis ($57 300 to $59 500).10

In the EP-guided arm of our study, the high mortality (7 patients, 64%) in the subgroup of patients who were discharged with antiarrhythmic drugs as sole therapy was remarkable.16 Of these 7 patients, 4 died suddenly despite the fact that drug treatment was thought to be effective from both noninvasive and invasive efficacy tests. This mortality rate is higher than that reported in some previous studies for suppression of inducibility with antiarrhythmic drug treatment.4 32 The methods used to assess therapy efficacy, including the programmed electric stimulation protocol, were current and in agreement with the methods described by others.4 16 19 23 32 33 34 In our present study of postinfarct sudden death survivors, however, these methods appeared unreliable in predicting long-term outcome. During the last 5 years, other reports have evolved that expressed doubt about the reliability of EP-guided drug testing.5 35 36 37 In addition to the results of our randomized study, we analyzed the influence on cost-effectiveness (1992 cost scenario) of three assumptions in the EP-guided strategy group: lower sudden death rate, therapy efficacy assessment without EP testing, and exclusion of VT surgery as a therapeutic option.

To study the effect of the poor outcome in patients with antiarrhythmic drugs as sole therapy on the cost-effectiveness ratio of the EP-guided strategy, we assumed an outcome similar to that reported previously for such patients.4 32 We estimated the cost-effectiveness ratio of the EP-guided arm if 3 patients who died suddenly would have stayed alive without readmissions until the end of the study. This would have resulted in a median cost-effectiveness ratio of the EP-guided strategy of $86 instead of $94 per patient per day alive (see Table 2Up) and a mean cost-effectiveness ratio of $81 instead of $87 per patient day alive (see Table 3Up).

Although in our opinion the results of the Electrophysiologic Study Versus Electrocardiographic Monitoring Study38 do not necessarily apply to our patient population, we have analyzed the influence on cost-effectiveness assuming a similar approach to therapy efficacy assessment. Therefore, cost-effectiveness ratios were estimated with the costs of EP studies in the patients of the EP-guided arm ignored. Then, the median and mean cost-effectiveness ratios in the EP-guided arm would have been $91 and $81 per patient per day alive, respectively.

Although we think that VT surgery may be a suitable therapy in selected patients and with appropriate surgical experience,24 25 39 we have also studied the effect of arrhythmia surgery on the cost-effectiveness ratio. For that purpose, we estimated the EP-guided cost-effectiveness ratio by disregarding the costs of surgery in the 6 patients with arrhythmia surgery and assuming that they would have had ICD implantation after drug failure and stayed alive without further costs until the end of the study. This resulted in median and mean cost-effectiveness ratios of the EP-guided arm of $89 and $86 per patient per day alive, respectively.

Thus, according to these assumptions, the median and mean cost-effectiveness ratios varied between $86 and $91 and between $81 and $86 per patient per day alive, respectively. These values are lower than those obtained in the EP-guided arm of the randomized study (see Tables 2Up and 3Up) but remain much higher than obtained with ICD implantation as first-choice treatment. It should be stressed, however, that such calculations are purely hypothetical and may therefore be different from those obtained from ongoing prospective comparative studies.40 41 42 43 44

Cost-effectiveness analyses of ICD implantation to date have been performed retrospectively.10 11 13 Kuppermann et al10 compared one group of patients discharged with ICDs implanted as a last resort with a group of patients treated with antiarrhythmic drugs. Other therapeutic options were not considered. They calculated a net cost-effectiveness ratio of $17 100 per life-year saved as extra costs for the ICD according to a 1986 scenario. They expected scenarios later than 1986 to be less costly on the basis of assumptions of increased longevity of the device and a transvenous approach to implantation. A similar expectation was expressed in the model study by Anderson and Camm13 in a 1993 report. Costs were also expected to be lower if the decision to implant the ICD had been made earlier. This latter aspect was retrospectively studied by O'Donoghue et al,11 who suggested a trend toward lower costs for such a strategy. The studies by Kuppermann et al10 and O'Donoghue et al11 were hampered by their retrospective characters and heterogeneous patient populations. In contrast, the present study involved comparable patient groups that were randomized after stratification according to left ventricular function and followed prospectively according to the intention-to-treat principle.16 In addition, important alternatives to drug therapy (eg, map-guided ablative techniques) that are part of the EP-guided therapeutic approach were not considered in the above retrospective analyses. By studying total mortality of a well-defined patient population in a randomized design, this study has overcome objections against comparisons of ICD therapy with "historical" controls, as recently raised by Zipes.41

In our study, all but three ICDs were implanted by transthoracic approach, which was the standard approach at the beginning of the study.16 At that time, there was limited experience with transvenous implantation. We later agreed that patients with previous cardiac surgery could have the transvenous approach. The transvenous approach has become the approach of choice in most patients, and morbidity and mortality are expected to decrease.28 45 46 47 48 49 50 This approach will rarely require postoperative care in an intensive care unit.51 Hence, these factors will result in shorter hospitalization, lower costs, and better cost-effectiveness. Technological advances, eg, devices of smaller size that may be implanted subpectorally in the EP laboratory,51 and increased longevity are further expected to add to superior cost-effectiveness of early ICD therapy.

Study Limitations
Within the context of our study design and the type of antiarrhythmic drugs chosen, ICD as first-choice therapy appears to be the most cost-effective approach. However, we cannot exclude that other strategies not investigated in our study may have similar or even better cost-effectiveness. Further studies comparing different scenarios (eg, empirical amiodarone or other EP-guided drugs) must be performed to confirm or complement the findings of our study. Such studies should be done before a definitive answer can be given as to whether an ICD as first-choice therapy should be routinely recommended in these patients. This issue may be solved by ongoing studies.40 41 42 43 44

The cost-effectiveness analysis did not include a consideration of nonmedical costs, eg, those created by patients' reduction of professional activities. For all studied patients, calculation of costs of diagnostic and therapeutic procedures was done according only to the lowest class scale rates of Dutch private healthcare insurance as used by the billing department of the University Hospital of Utrecht, which may not always have covered all costs incurred. During the study period, six pulse generators had to be replaced because of end-of-life situations with no effect on the cost-effectiveness ratio. The relatively short duration of the study did not allow an appropriate estimation of the influence of more replacements over time.

Conclusions
Data from this randomized study demonstrate that in terms of cost-effectiveness early ICD implantation is superior to serial drug testing and subsequent EP-guided, nonpharmacological therapy as used in this study in postinfarct sudden death survivors. This is in accordance with the expectation expressed in retrospective studies. Immediate implantation after judicious decision making, use of transvenous leads, and refinement of ICD technology may add to improve cost-effectiveness of ICD therapy. Finally, results of this study originate from a first attempt at a synthesis between clinical, scientific, and economic data. Cooperative efforts in these three fields may contribute to political decision making and reimbursement policy.


*    Selected Abbreviations and Acronyms
 
EP = electrophysiology
ICD = implantable cardioverter-defibrillator
NYHA = New York Heart Association
VF = ventricular fibrillation
VT = ventricular tachycardia


*    Acknowledgments
 
This work was supported by the Dutch Sick-Fund Council and Cardiac Pacemakers Inc. We are indebted to Fred Wittkampf, PhD, Ans Wiesfeld, MD, Alice Ester, MD, and Erik Buskens, MD, for their support in data analysis and to Judith van Gestel and Barbara Holderbusch for their help in preparing the manuscript.

Received May 22, 1995; revision received September 11, 1995; accepted September 17, 1995.


*    References
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
up arrowDiscussion
*References
 

  1. Skale BT, Miles WM, Heger JJ, Zipes DP, Prystowsky EN. Survivors of cardiac arrest: prevention of recurrence by drug therapy as predicted by electrophysiologic testing or electrocardiographic monitoring. Am J Cardiol. 1986;57:113-119. [Medline] [Order article via Infotrieve]
  2. Waller TJ, Kay HR, Spielman SR, Kutalek SP, Greenspan AM, Horowitz LM. Reduction in sudden death and total mortality by antiarrhythmic therapy evaluated by electrophysiologic drug testing: criteria of efficacy in patients with sustained ventricular tachycardia. J Am Coll Cardiol. 1987;10:83-89. [Abstract]
  3. Eldar M, Sauve MJ, Scheinman MM. Electrophysiologic testing and follow-up of patients with aborted sudden death. J Am Coll Cardiol. 1987;10:291-298. [Abstract]
  4. Wilber DJ, Garan H, Finkelstein D, Kelly E, Newell J, McGovern B, Ruskin JN. Out-of-hospital cardiac arrest: use of electrophysiologic testing in the prediction of long-term outcome. N Engl J Med. 1988;318:19-24. [Abstract]
  5. Knilans TK, Prystowsky EN. Antiarrhythmic drug therapy in the management of cardiac arrest survivors. Circulation. 1992;85(suppl I):I-118-I-124.
  6. Mirowski M, Reid PR, Winkle RA, Mower MM, Watkins L Jr, Stinson EB, Griffith LSC, Kallman CH, Weisfeldt ML. Mortality in patients with implanted automatic defibrillators. Ann Intern Med. 1983;98:585-588.
  7. Echt DS, Armstrong K, Schmidt P, Oyer PE, Stinson EB, Winkle RA. Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator. Circulation. 1985;71:289-296. [Abstract/Free Full Text]
  8. Fogoros N, Elson JJ, Bonnet CA, Fiedler SB, Burkholder JA. Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease. J Am Coll Cardiol. 1990;16:381-386. [Abstract]
  9. Akhtar M, Avitall B, Jazayeri M, Tchou P, Troup P, Sra J, Axtell K. Role of implantable cardioverter defibrillator therapy in the management of high-risk patients. Circulation. 1992;85(suppl I):I-131-I-139.
  10. Kuppermann M, Luce BR, McGovern B, Podrid PJ, Bigger JT Jr, Ruskin JN. An analysis of the cost effectiveness of the implantable defibrillator. Circulation. 1990;81:91-100. [Abstract/Free Full Text]
  11. O'Donoghue S, Platia EV, Brooks-Robinson S, Mispireta L. Automatic implantable cardioverter-defibrillator: is early implantation cost-effective? J Am Coll Cardiol. 1990;16:1258-1263. [Abstract]
  12. Saksena S, Camm AJ. Implantable defibrillators for prevention of sudden death: technology at a medical and economic crossroad. Circulation. 1992;85:2316-2321. Editorial. [Abstract/Free Full Text]
  13. Anderson MH, Camm AJ. Implications for present and future applications of the implantable cardioverter-defibrillator resulting from the use of a simple model of cost efficacy. Br Heart J. 1993;69:83-92. [Abstract/Free Full Text]
  14. Wever EFD, Hauer RNW, Crijns HJGM, Van Capelle FJL, Robles de Medina EO. Antiarrhythmic drugs as first option not warranted in survivors of cardiac arrest late after myocardial infarction. Circulation. 1993;88:I-118. Abstract.
  15. Wever EFD, Hauer RNW, Crijns HJGM, Van Capelle FJL, Bakker PFA, Robles de Medina EO. Randomized study of conventional strategy versus implantable defibrillator as first-choice therapy in postinfarct sudden death survivors. Circulation. 1993;88(suppl I):I-156. Abstract.
  16. Wever EFD, Hauer RNW, Van Capelle FL, Tijssen JGP, Crijns HJGM, Algra A, Wiesfeld ACP, Bakker PFA, Robles de Medina EO. Randomized study of implantable defibrillator as first-choice therapy versus conventional strategy in postinfarct sudden death survivors. Circulation. 1995;91:2195-2203. [Abstract/Free Full Text]
  17. O'Rourke RA. Current trends in clinical cardiology: a march of folly? Circulation. 1987;75:1097-1101. Editorial. [Free Full Text]
  18. Sweeney MO, Ruskin JN. Mortality benefits and the implantable cardioverter-defibrillator. Circulation. 1994;89:1851-1858. [Abstract/Free Full Text]
  19. Wever EFD, Hauer RNW. Cost-effectiveness considerations: the Dutch prospective study of the automatic implantable cardioverter defibrillator as first-choice therapy. PACE Pacing Clin Electrophysiol. 1992;15:690-693. [Medline] [Order article via Infotrieve]
  20. Tchou PJ, Kadri N, Anderson J, Caceres JA, Jazayeri M, Akhtar M. Automatic implantable cardioverter defibrillators and survival of patients with left ventricular dysfunction and malignant ventricular arrhythmias. Ann Intern Med. 1988;109:529-534.
  21. Hauser RG. The cost of tachyarrhythmia management. Arch Mal Coeur Vaiss. 1985;78:35-37.
  22. Krucoff M, Chu F, McCallum D, Perry S. New medical technologies in a cost containment environment: implantable antitachyarrhythmia devices. PACE Pacing Clin Electrophysiol. 1987;10:2-20. [Medline] [Order article via Infotrieve]
  23. Wever EFD, Hauer RNW, Oomen A, Peters RHJ, Bakker PFA, Robles de Medina EO. Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation. Circulation. 1993;88:1021-1029. [Abstract/Free Full Text]
  24. Garan H, Nguyen K, McGovern B, Buckley M, Ruskin JN. Peri-operative and long-term results after electrophysiologically directed ventricular surgery for recurrent ventricular tachycardia. J Am Coll Cardiol. 1986;8:201-209. [Abstract]
  25. Van Hemel NM, Kingma JH, Defauw JAM, Vermeulen FE, Mast EG, Ernst JM, Ascoop CA. Left ventricular segmental wall motion score as a criterion for selecting patients for direct surgery in the treatment of postinfarction ventricular tachycardia. Eur Heart J. 1989;10:304-315. [Abstract/Free Full Text]
  26. Willems AR, Tijssen JGP, Van Capelle FJL, Kingma JH, Hauer RNW, Vermeulen FEE, Brugada P, Van Hoogenhuyze DCA, Janse MJ. Determinants of prognosis in symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction. J Am Coll Cardiol. 1990;16:521-530. [Abstract]
  27. Warner KE, Luce BR. Principles: the methodology of CBA-CEA. Cost-Benefit and Cost-Effectiveness Analysis in Health Care: Principles, Practice, and Potential. Ann Arbor, Mich: Health Administration Press; 1982:92.
  28. Kupersmith J, Holmes-Rovner M, Hogan A, Rovner D, Gardiner J. Cost-effectiveness analysis in heart disease, part I: general principles. Prog Cardiovasc Dis. 1994;37:161-184. [Medline] [Order article via Infotrieve]
  29. Jung W, Manz M, Deister A, Lüderitz B. Quality of life in ICD recipients. Circulation. 1994;90(suppl I):I-499. Abstract.
  30. Kim SG, Fisher JD, Furman S, Gross J, Zilo P, Roth JA, Ferrick KJ, Brodman R. Benefits of implantable defibrillators are overestimated by sudden death rates and better represented by the total arrhythmic death rate. J Am Coll Cardiol. 1991;17:1587-1592. [Abstract]
  31. Henthorn RW, Waller TJ, Hiratzka LF. Are the benefits of the automatic implantable cardioverter-defibrillator overestimated by sudden death rate? J Am Coll Cardiol. 1991;17:1593-1594. Editorial. [Medline] [Order article via Infotrieve]
  32. Ruskin JN, DiMarco JP, Garan H. Out-of-hospital cardiac arrest: electrophysiologic observations and selection of long-term antiarrhythmic therapy. N Engl J Med. 1980;303:607-613. [Abstract]
  33. Denker S, Lehmann M, Mahmud R, Gilbert C, Akhtar M. Facilitation of ventricular tachycardia induction with abrupt changes in cycle length. Am J Cardiol. 1984;53:508-515. [Medline] [Order article via Infotrieve]
  34. Ruskin JN. Role of invasive electrophysiological testing in the evaluation and treatment of patients at high risk for sudden cardiac death. Circulation. 1992;85(suppl I):I-152-I-159.
  35. Poole JE, Mathisen TL, Kudenchuk PJ, McAnulty JH, Swerdlow CD, Bardy GH, Greene HL. Long-term outcome in patients who survive out of hospital ventricular fibrillation and undergo electrophysiologic studies: evaluation by electrophysiologic subgroups. J Am Coll Cardiol. 1990;16:657-665. [Abstract]
  36. Kim SG. Management of survivors of cardiac arrest: is electrophysiologic testing obsolete in the era of implantable defibrillators? J Am Coll Cardiol. 1990;16:756-762. Editorial. [Medline] [Order article via Infotrieve]
  37. Wasilewski SJ, Ferrick KJ, Borgen E, Roth JA, Kim SG, Fisher JD. The role of serial drug testing in patients with inducible polymorphic ventricular tachycardia. Pacing Clin Electrophysiol. 1994;17:830. Abstract.
  38. Mason JW, for the ESVEM Investigators. A comparison of electrophysiologic testing with Holter monitoring to predict antiarrhythmic drug efficacy for ventricular tachyarrhythmias. N Engl J Med. 1993;329:445-451. [Abstract/Free Full Text]
  39. DiMarco JP. Management of sudden cardiac death survivors: role of surgical and catheter ablation. Circulation. 1992;85(suppl I):I-125-I-130.
  40. Epstein AE. AVID necessity. PACE Pacing Clin Electrophysiol. 1993;16:1773-1775. [Medline] [Order article via Infotrieve]
  41. Zipes DP. Implantable cardioverter-defibrillator: lifesaver or a device looking for a disease? Circulation. 1994;89:2934-2936. Editorial. [Free Full Text]
  42. Zipes DP. Are implantable cardioverter-defibrillators better than conventional antiarrhythmic drugs for survivors of cardiac arrest? Circulation. 1995;9:2115-2117. Editorial.
  43. Conolly SJ, Jent M, Roberts RS, Dorian P, Green MS, Klein GJ, Mitchell LB, Sheldon RS, Roy D. Canadian Implantation Defibrillator Study (CIDS): study design and organization. Am J Cardiol. 1993;72:103F-108F. [Medline] [Order article via Infotrieve]
  44. Siebels J, Kuck KH. Implantable cardioverter defibrillator compared with antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac Arrest Study Hamburg). Am Heart J. 1994;127:1139-1144. [Medline] [Order article via Infotrieve]
  45. Becker D, Block M, Isbruch F, Wietholt D, Hammel D, Borggrefe M, Breithardt G. Do patients with an implantable defibrillator live longer? J Am Coll Cardiol. 1993;21:1638-1644. [Abstract]
  46. Block M, Hammel D, Borggrefe M, Isbruch F, Wietholt D, Hachenberg T, Scheld HH, Breithardt G. Transvenous-subcutaneous implantation of defibrillators as the approach of first choice. Circulation. 1991;84(suppl II):II-427. Abstract.
  47. Guarnieri T, Cannom DS, Chapman PD, Chilson DA, Echt D S, Epstein AE, Furman S, Greer GS, Luceri RM, Maloney JD, Parsonnet V, Prystowsky EN, Ruskin JN, Veltri EP, Winkle RA. Multicenter experience: transvenous implantable cardioverter defibrillator lead system. Circulation. 1991;84(suppl II):II-428. Abstract.
  48. Saksena S, for the PCD Investigator Group. Clinical outcome of patients with malignant ventricular tachyarrhythmias and a multiprogrammable implantable cardioverter-defibrillator with or without thoracotomy: an international multicenter study. J Am Coll Cardiol. 1994;23:1521-1530. [Abstract]
  49. Neuzner J, for the European Ventak P2 Investigator Group. Clinical experience with a new cardioverter defibrillator capable of biphasic waveform pulse and enhanced data storage: results of a prospective multicenter study. Pacing Clin Electrophysiol. 1994;17:1243-1255. [Medline] [Order article via Infotrieve]
  50. Strickberger SA, Hummel JD, Daoud E, Niebauer M, Williamson BD, Man KC, Horwood L, Schmittou A, Kalbfleisch SJ, Langberg JJ, Morady F. Implantation by electrophysiologists of 100 consecutive cardioverter defibrillators with nonthoracotomy lead systems. Circulation. 1994;90:868-872. [Abstract/Free Full Text]
  51. Fitzpatrick AP, Lesh MD, Epstein LM, Lee RJ, Siu A, Merrick S, Griffin JC, Scheinman MM. Electrophysiological laboratory, electrophysiologist-implanted, nonthoracotomy-implantable cardioverter/defibrillators. Circulation. 1994;89:2503-2508.[Abstract/Free Full Text]



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