Abstract

Implantable cardioverter-defibrillator (ICD) therapy has emerged as the most effective treatment for life-threatening ventricular arrhythmias. Most studies indicate that ICD therapy in appropriately selected patients at high risk of sudden cardiac death (SCD) is associated with cost-effectiveness ratios similar to, or better than, other accepted treatments, including renal dialysis. The up-front costs of ICD therapy are admittedly high and as such, ICD implantation is more akin to an operation than a drug. As would be the case for a life-saving operation, the adoption of short time horizons is apt to lead to underestimations of cost effectiveness. As well as the time horizon, the underlying aetiology of the arrhythmic substrate, implantation technique, ICD battery life, and the presence of co-morbidities are important issues in maximizing cost effectiveness. Above all, we should consider that ICD therapy is the only available option for prolonging survival in patients who are at risk of SCD.

Introduction

Sudden cardiac death (SCD) accounts for more deaths than stroke, breast and lung cancer, and acquired immunodeficiency syndrome combined.1 The principal cause of SCD is ventricular tachyarrhythmia, namely ventricular tachycardia (VT) and ventricular fibrillation (VF). Antiarrhythmic drugs once held promise as therapeutic options for patients with ventricular tachyarrhythmias but over the past 30 years, however, resulted to exert a neutral or even negative effect on survival.

Since its introduction by Mirowski et al.2 in 1980, implantable cardioverter-defibrillator (ICD) therapy has emerged as the most effective treatment for life-threatening ventricular arrhythmias. The ICD has evolved from a large device requiring a thoracotomy for lead placement and an abdominal pocket for device implantation, to a transvenous procedure with transvenous lead deployment. Emerging evidence from randomized controlled trials has paved the way for an exponential growth in the use of this life-saving therapy.

In its early days, ICD therapy was limited to few patients who had already succumbed to ventricular tachyarrhythmia. Over the past decade, however, ICD therapy, either alone or in combination with cardiac resynchronization therapy, has been extended to the primary and secondary prevention of SCD in patients with coronary heart disease and/or heart failure. In fact, primary prevention of SCD in patients with heart failure or asymptomatic left ventricular dysfunction is now the principal indication of ICD therapy. Accordingly, the demand for ICD therapy is likely to parallel the increasing prevalence of heart failure that currently stands at ∼2% of the general population.3 The demand for ICD therapy will rise further with an ageing population and the improved survival with treatments such as revascularization.

For any healthcare system, an increasing demand for a costly therapy begs scrutiny of clinical efficacy and cost effectiveness. On the one hand, the clinician's principal concern is the individual patient. On the other, is the Public Health's concern with society as a whole, even when benefit to society comes at a loss to the individual.4 In the melting pot of a healthcare system comprising clinicians, public health physicians, economists, commissioners, managers and politicians, a difficult choice exists between what is good for the individual, and what society can afford.4,5 Cost effectiveness is not the only basis on which a therapy should be commissioned, but it is helpful in deciding whether it is financially viable, particularly if there are competing therapies. This review focuses on the cost effectiveness of ICD therapy, in the context of both the primary and secondary prevention. Factors that influence cost effectiveness are also discussed.

Willingness to pay

In the USA, the willingness to pay for medical therapies has traditionally been based on the cost of renal dialysis, which approximated to $40 000 (€28 736) per patient per year in 2002.6,7 Treatments with incremental cost-effectiveness ratios (ICERs) <$50 000 (€35 920) are usually considered acceptable; those exceeding $100 000 (€71 840) are considered too expensive, and; those between $50 000 and $100 000 are considered borderline.8 A figure for Europe is difficult to ascertain, but the consensus suggests a benchmark of €40 000 ($55 677).5 In the UK, the National Institute of Clinical Excellence (NICE) is unlikely to reject a technology with an ICER per quality-adjusted life year (QALY) ≤ British £15 000 (€17 100) and would require special reasons for supporting technologies with ICERs > £30 000 (€34 200) (Currency conversion: 1€ = US$1.39 or C$1.42 or £0.88.)

The decision of a healthcare system to fund a treatment is influenced by clinical guidelines. Generally, clinical guideline groups rely solely on the scientific and clinical evidence available. In the UK, NICE, also considers cost effectiveness in its recommendations. It is perhaps not a coincidence that NICE guidelines on ICD therapy are the most restrictive.

Secondary prevention

Most emerging therapies are first evaluated in high-risk patient populations. Accordingly, the efficacy of ICD therapy was initially assessed in patients who had suffered an arrhythmic event. Three trials assessed the clinical efficacy of ICD therapy in the secondary prevention of SCD, namely the Antiarrhythmics vs. Implantable Defibrillators (AVID) trial,9 the Cardiac Arrest Study Hamburg (CASH),10 and the Canadian Implantable Defibrillator Study (CIDS).11 In AVID, ICD therapy was associated with a 31% reduction in total mortality, compared with amiodarone.9 In CASH, ICD therapy was associated with a non-significant 23% reduction in mortality, compared with the amiodarone/metoprolol arm.10 In CIDS, ICD therapy was associated with a non-significant 19.7% relative risk reduction [95% confidence interval (CI), −7.7 to 40%; P= 0.142] in all-cause mortality, compared with amiodarone.11 Although CASH and CIDS did not reach statistical significance in the pre-defined endpoints, a meta-analysis of AVID, CASH, and CIDS12 showed that ICD therapy, as compared with drug therapy, was associated with a marked reduction in arrhythmic death [hazard ratio (HR) 0.50 (95% CI 0.37, 0.67), P< 0.0001] and total mortality [HR 0.72 (95% CI 0.60, 0.87)] (Table 1).

Table 1

Inclusion criteria and efficacy of implantable cardioverter defibrillator in secondary prevention studies

Study Inclusion criteria Efficacy of ICD (total mortality)a 
AVID Resuscitation from VF or VT arrest or sustained VT with syncope, or sustained VT with haemodynamic compromise and LVEF <40% 0.62 (0.47, 0.81) 
CIDS No MI in preceding 72 h plus any of the following: VF; out-of hospital cardiac arrest requiring defibrillation or cardioversion; sustained syncopal VT; sustained VT (≥150 bpm) with presyncope or angina and LVEF ≤35%; unmonitored syncope and subsequent VT >10 s or sustained monomorphic VT ≥30 s on VT induction 0.82 (0.61, 1.10) 
CASH No MI in preceding 72 h plus resuscitation from VF or VT arrest 0.83 (0.52, 1.33) 
All (meta-analysis)  0.72 (0.60, 0.87) 
Study Inclusion criteria Efficacy of ICD (total mortality)a 
AVID Resuscitation from VF or VT arrest or sustained VT with syncope, or sustained VT with haemodynamic compromise and LVEF <40% 0.62 (0.47, 0.81) 
CIDS No MI in preceding 72 h plus any of the following: VF; out-of hospital cardiac arrest requiring defibrillation or cardioversion; sustained syncopal VT; sustained VT (≥150 bpm) with presyncope or angina and LVEF ≤35%; unmonitored syncope and subsequent VT >10 s or sustained monomorphic VT ≥30 s on VT induction 0.82 (0.61, 1.10) 
CASH No MI in preceding 72 h plus resuscitation from VF or VT arrest 0.83 (0.52, 1.33) 
All (meta-analysis)  0.72 (0.60, 0.87) 

VT induction, ventricular tachycardia induction test; VF, ventricular fibrillation; VT, ventricular tachycardia; LVEF, left ventricular ejection fraction; MI, myocardial infarction. For description of acronyms and references, see text.

aEfficacy of ICD therapy compared with drug therapy is expressed in terms of hazard ratios (95% confidence intervals). Modified with permission from Connolly et al.12

The cost effectiveness of ICD therapy in AVID was explored by Larsen et al.,13 who prospectively compared the costs of ICD therapy with antiarrhythmic therapy (mostly amiodarone). The time horizon used for the primary intention-to-treat cost-effectiveness analysis was the 3-year duration of the trial. In a second analysis, 20-year and lifetime cost-effectiveness evaluations were undertaken. Both life years (LYs) and cost were discounted at 3%. At 3 years of follow-up, the expected survival for patients treated with ICDs was 0.21 years longer than for antiarrhythmic drug therapy. At an incremental cost of $14 101 (€10 130), ICD therapy was associated with an ICER of $66 677 (€47 901) per LY saved (LYS). In sensitivity analyses, the ICER per LYS was $55 163 (€39 629) for a patient with VF and $82 884 (€59 543) for a patient with VT. The ICER per LYS was lower in patients with a left ventricular ejection fraction (LVEF) ≤35% ($60 967; €43 799), compared with patients with a LVEF >35% ($536 106; €385 139). Age did not appear to influence the ICER.

A cost-effectiveness analysis of CIDS yielded an ICER of C$213 543 (€150 680) per LYS from ICD therapy, as compared with amiodarone.14 This is perhaps not surprizing, as the CIDS trial itself failed to show a mortality benefit from ICD therapy (0.23 years longer than the patients in the amiodarone arm). Moreover, 34% of ICD patients in CIDS underwent ICD generator replacements during the 6.3 years of trial follow-up, which is considerably higher than 7% in AVID over 3 years of follow-up.

Primary prevention

Following the demonstration that ICD therapy was effective in secondary prevention, efforts were focused on its application in primary prevention. The most authoritative cost-effectiveness analysis of ICD therapy in the primary prevention of SCD was provided by Sanders et al.15 Eight landmark ICD trials, namely the Coronary Artery Bypass Graft (CABG) Patch Trial,16 the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT),17 the Multicentre Automatic Defibrillator Implantation Trial (MADIT),18 MADIT-II,19 the Multicenter Unsustained Tachycardia Trial (MUSTT),20 the Defibrillators in Non-Ischaemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial,21 the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial,22 and the SCD in Heart Failure Trial (SCD-HeFT)23 were considered (Table 2). A Markov model of the cost, quality of life, survival, and incremental cost effectiveness was used to compare ICD therapy to control therapy over a lifetime horizon. The model assumed that the probability of death was constant identical to the total rate of death from any cause in the control group. Hazard ratios reported in the individual trials were used to model efficacy and cost effectiveness. Quality of life was assumed not to change following ICD implantation. As expected, the lack of clinical efficacy of ICD therapy in the CABG-Patch and the DINAMIT studies translated to a lack of cost effectiveness over control therapy. In the case of the six other trial populations, ICD improved life expectancy, with the discounted increment ranging from 1.40 to 4.14 years (1.01–2.99 QALYs). On this basis, the base-case ICERs ranged from $34 000 (€24 426) to $70 000 (€50 288) per QALY. In sensitivity analyses, reducing the cost of an ICD from $27 975 (€20 097) to $10 000 (€7184) was associated with an improvement in the ICER from $70 200 (€50 432) to $52 400 (€37 644) per QALY in SCD-HeFT and from $34 000 (€24 426) to $27 900 (€20 043) per QALY in MUSTT. Importantly, the cost effectiveness of ICD therapy as compared with control therapy was <$100 000 (€71 840) in all trial populations, as long as the effectiveness of the ICD was assumed to continue for at least 7 years.

Table 2

Inclusion criteria and efficacy of implantable cardioverter-defibrillator in primary prevention studies

Study Inclusion criteria Efficacy of ICD (total mortality)a 
MADIT-I MI three weeks or more before study; NSVT, and; LVEF ≤35% 0.46 (0.26, 0.82) 
CABG-Patch Scheduled for CABG; LVEF ≤35%, and abnormalities on SAECG 1.07 (0.81, 1.42) 
MUSTT CAD, LVEF ≤40%, and asymptomatic non-sustained VT within 6 months and not within 4 days after a MI or CABG 0.45 (0.32, 0.63) 
MADIT-II MI one month or more before study, and LVEF ≤30% 0.69 (0.51, 0.93) 
DEFINITE LVEF ≤35%; premature ventricular complexes or NSVT; symptomatic heart failure, and non-ischaemic cardiomyopathy 0.65 (0.40, 1.06) 
COMPANION NYHA III or IV; LVEF ≤35%; QRS ≥120 ms; PR >150 ms; sinus rhythm, and hospitalization for the treatment of CHF in preceding 12 months 0.64 (0.48, 0.86) 
DINAMIT Within 4–40 days of a MI; LVEF ≤35%, and impaired autonomic tone by heart rate variability 1.08 (0.76, 1.55) 
SCD-HeFT NYHA class II or III symptoms; LVEF ≤35%, and optimal medical therapy 0.77 (0.62, 0.96) 
Study Inclusion criteria Efficacy of ICD (total mortality)a 
MADIT-I MI three weeks or more before study; NSVT, and; LVEF ≤35% 0.46 (0.26, 0.82) 
CABG-Patch Scheduled for CABG; LVEF ≤35%, and abnormalities on SAECG 1.07 (0.81, 1.42) 
MUSTT CAD, LVEF ≤40%, and asymptomatic non-sustained VT within 6 months and not within 4 days after a MI or CABG 0.45 (0.32, 0.63) 
MADIT-II MI one month or more before study, and LVEF ≤30% 0.69 (0.51, 0.93) 
DEFINITE LVEF ≤35%; premature ventricular complexes or NSVT; symptomatic heart failure, and non-ischaemic cardiomyopathy 0.65 (0.40, 1.06) 
COMPANION NYHA III or IV; LVEF ≤35%; QRS ≥120 ms; PR >150 ms; sinus rhythm, and hospitalization for the treatment of CHF in preceding 12 months 0.64 (0.48, 0.86) 
DINAMIT Within 4–40 days of a MI; LVEF ≤35%, and impaired autonomic tone by heart rate variability 1.08 (0.76, 1.55) 
SCD-HeFT NYHA class II or III symptoms; LVEF ≤35%, and optimal medical therapy 0.77 (0.62, 0.96) 

ICD, implantable cardioverter-defibrillator; MI, myocardial infarction; NSVT, non-sustained ventricular tachycardia; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association class; SAECG, signal averaged echocardiogram; CHF, chronic heartfailure. For description of acronyms and references, see text.

aEfficacy of ICD compared with drug therapy expressed as hazard ratio (95% confidence intervals).

North American cost-effectiveness analyses may not be generalizable to European heathcare systems. In this light, Cowie et al.24 modelled the lifetime cost effectiveness of primary prevention ICD therapy based on Belgian reimbursement costs and on a meta-analysis of the following studies: the amiodarone vs. implantable cardioverter-defibrillator randomized trial in patients with non-ischaemic dilated cardiomyopathy and asymptomatic non-sustained ventricular tachycardia (AMIOVIRT) study,25 the Cardiomyopathy Trial (CAT),26 DEFINITE,21 MADIT,18 MADIT II,19 and SCD-HeFT.23 The analysis was based on Sanders et al.'s15 model of the cost effectiveness of ICD. Incremental cost-effectiveness ratios were estimated based on direct medical costs, LYs, and QALYs gained. All analyses were from the Belgian healthcare system perspective over patients’ lifetimes. The base-case analysis was based on a cost of €16 650 ($23 176) for a de novo or replacement single-chamber ICD [plus €1772 ($2466) for the leads] and €4650 ($6472) for the initial implantation. Costs of complications, follow-up, and medication were also Belgian specific. In the meta-analysis, ICD therapy was associated with a significant reduction in the risk of SCD [relative risk (RR) 0.37 (95% CI 0.28, 0.48)] and all-cause mortality [RR of 0.72 (95% CI 0.64, 0.82)]. In a deterministic base-case analysis, ICD therapy for primary prevention was associated with an average additional gain of 2.22 years over conventional therapy, reduced SCDs by ∼50% and improved QALY relative to conventional therapy (discounted value of 1.57 years), at an additional cost of €46 413 ($64 604) (Table 3). For patients aged 61 years, the estimated ICER of ICD therapy compared with conventional therapy was €24 751 ($34 451) per LYS and €29 530 ($41 104) per QALY. In deterministic sensitivity analyses, the ICER of ICD therapy was most sensitive to its clinical efficacy. Other significant influences on the ICER included ICD battery life and age at the time of device implantation. Surprizingly, the ICER was least sensitive to varying device cost. The ICERs were in the range of €13 727 ($19 107) to €37 363 ($52 007) for all values tested.

Table 3

Lifetime cost-effectiveness ratios for implantable cardioverter-defibrillator therapy for primary prevention of sudden cardiac death, compared with conventional therapy

Intervention LYS QALY Cost (€) ICER (€/LYS) ICER (€/QALY) 
Discounted      
 ICD 8.58 7.27 64 600 24 751 29 530 
 Conventional therapy 6.71 5.70 18 187   
 Difference 1.88 1.57 46 413   
Undiscounted      
 ICD 9.52 8.06 75 262 24 271 29 009 
 Conventional therapy 7.30 6.20 21 366   
 Difference 2.22 1.86 53 896   
Intervention LYS QALY Cost (€) ICER (€/LYS) ICER (€/QALY) 
Discounted      
 ICD 8.58 7.27 64 600 24 751 29 530 
 Conventional therapy 6.71 5.70 18 187   
 Difference 1.88 1.57 46 413   
Undiscounted      
 ICD 9.52 8.06 75 262 24 271 29 009 
 Conventional therapy 7.30 6.20 21 366   
 Difference 2.22 1.86 53 896   

Deterministic base-case analysis: ICD, implantable cardioverter-defibrillator; ICER, incremental cost-effectiveness ratio; LYS, life years saved; QALY, quality-adjusted life years. Reproduced with permission from Cowie M, et al.24

Factors influencing cost effectiveness

The ‘base-case’ in cost-effectiveness analyses reflects the patient characteristics, device technology, implantation techniques, post-operative care, medical therapy, and long-term follow-up that are considered current at the time of the analyses. To make these analyses relevant, it is imperative that all the current characteristics of device therapy are taken into account. For example, much of the cost-effectiveness data reviewed above have emerged from patients with devices implanted prior to 1990, at a time of intra-abdominal implantations and prolonged post-operative were the rule. These analyses, however, are of questionable relevance in the days of transvenous lead deployment and subcutaneous device implantation. In the following account, we discuss factors that may influence the current and future cost effectiveness of ICD therapy.

Time horizon

In cost-effectiveness analysis of two competing strategies, the choice of time horizon has a substantial effect on ICERs. In this respect, a review of eight trials has shown that the benefit from ICD therapy increases non-linearly with the square of time (Figure 1).27 This implies that at 3 years, the LYS per ICD implanted in trials such as MADIT,18 AVID,9 and CIDS,11 were 4.6, 4.4, and 9 times that observed at 1 year, respectively. Similar findings emerged from the 11-year follow-up of a subset of patients in the CIDS study28 and from the extended follow-up of MADIT-II.25

Figure 1

Time-dependent mortality benefit from implantable cardioverter-defibrillator therapy. *observed benefit at each time point as a proportion of the benefit gained at 3 years. Brown line shows the best-fit power-law relationship. Modified with permission from Salukhe et al.27

Figure 1

Time-dependent mortality benefit from implantable cardioverter-defibrillator therapy. *observed benefit at each time point as a proportion of the benefit gained at 3 years. Brown line shows the best-fit power-law relationship. Modified with permission from Salukhe et al.27

The increase in benefit from ICD therapy with time from implantation has important implications for its cost effectiveness, particularly as the therapy involves high up-front costs. In the SCD-HeFT study, the base-case lifetime ICER was $38 389 (€27 579) per QALY. Model projections revealed that the ICER per LYS was reduced from $209 530 (€150 526) at 5 years, and to $50 000 (€35 920) at 14 years.29 Short time horizons and cost-effectiveness model assumptions that the benefit of ICD therapy remains constant with time may therefore lead to an underestimation the true clinical benefit as well cost effectiveness. Studies which assume a fixed time horizon regardless of the clinical perspective or underlying pathology30 may underestimate the clinical efficacy and, therefore, the cost effectiveness of ICDs.

Implantation

The implantation costs for ICDs vary considerably between studies. In 1997, Owens et al.31 adopted an implantation cost figure of $44 600 (€32 041; including device and implantation), which was based on a survey of hospitals in North California. Cowie et al.,24 however, recently used a figure of €23 072 ($32 115), based on Belgium reimbursement rates. Such wide variations in implantation costs preclude the generalization of cost-effectiveness data worldwide.

Some of the ICDs implanted in studies that were subsequently included in cost-effectiveness analyses required a thoracotomy and abdominal pockets. This is in contrast with currently available ICDs, which can be <35cm3 in size and be implanted intravenously. In addition, modern ICDs are also capable of antitachycardia pacing, which can terminate VT and avoid shocks. In the meta-analysis of secondary prevention trials, Connolly et al.12 showed that epicardial ICD implantation was associated with no mortality benefit [HR 1.52 (95% CI 0.92–2.50)], whereas transvenously implanted ICDs were associated with a benefit [HR 0.69 (0.56–0.85), 0.029]. The effects of varying ICD size and functionality on quality of life have not been formally assessed. They are, however, likely to be relevant to cost effectiveness.

Advances in ICD hardware and implantation techniques also affect the length of stay in hospital. For example, the average length of stay during the secondary prevention AVID trial decreased from 15 days at the beginning of the trial to 10 days towards the end.9,13 For elective patients, there is today an increasing tendency to perform the implantation on a day case basis. Reductions in lengths of stay in hospital are likely to improve the cost effectiveness of ICD therapy.

Risk stratification

The cost-effectiveness ICD therapy can be maximized if it is targeted to those who are most likely to suffer life-threatening arrhythmic events. With respect to secondary prevention, analyses of the AVID study showed that the relative benefit of ICD therapy over medical therapy was limited to patients with a LVEF <35%.9 In the primary prevention study MADIT, the benefit from ICD therapy was mainly in patients with an LVEF ≤25%.32

The severity of the underlying cardiac disease may also be so extreme that patients die before they derive a benefit from ICDs. An elderly patient with severe heart failure might benefit less from ICD therapy, simply because pump failure may ensue before the development of a treatable arrhythmia. Setoguchi et al.33, who undertook a retrospective analysis of 14 374 patients with a first admission for heart failure, found that the maximum potential benefit of preventing SCD with ICD therapy was least in patients with co-morbidities or multiple admissions for heart failure. These findings indicate that patients with severe symptomatic heart failure [New York Heart Association (NYHA) class IV] or with frequent hospitalizations die from cardiac pump failure before they succumb to a treatable ventricular tachyarrhthymia.

Although selecting the ‘sicker’ patients may maximize the cost effectiveness of ICD therapy, the ‘less sick patients’ should not be overlooked. In this respect, an analysis of the SCD-HeFT primary prevention study, the benefit of ICD therapy was beneficial in patients in NYHA class II and not in patients in NYHA class III.23 The meta-analysis of primary prevention trials undertaken by Cowie et al.24 revealed a U-shaped relationship between the ICER and annual mortality for the conventional therapy group. The ICER for ICD therapy was less cost effective when the annual mortality rate in the conventional therapy group was low. The ICER, however, decreased as the annual mortality rate increased, to reach a nadir at ∼12.5% annual mortality. The ICER then increased with further increases in mortality rate rose.24

Aetiology

The meta-analyses on which cost-effectiveness analyses are based generally classify cardiomyopathies into ischaemic and non-ischaemic types, without further specification. Implantable cardioverter-defibrillator trials on primary prevention of SCD were included by Cowie et al.24 in a meta-analysis on which cost-effectiveness analyses were calculated, but aetiology was not included in sensitivity analyses. With regard to secondary prevention, only ≤15% patients included in AVID, CASH, or CIDS had non-ischaemic cardiomyopathy and in the meta-analysis,12 aetiology did not influence the outcome of ICD therapy.

Comparative cost effectiveness of implantable cardioverter-defibrillator therapy

Cost effectiveness is an important tool in the economic evaluation of healthcare technologies. Generally, therapies that are associated with the lowest ICERs are adopted. Therapies with ICERs that are clearly above the willingness to pay threshold have nevertheless been widely adopted in clinical practice (Table 4).34 Angiotensin-converting enzyme (ACE) inhibitors, for example, are recommended as first-line treatment for patients <55 years of age, even in the absence of other cardiovascular risk factors, but in this context, however, the ICER per QALY for ACE inhibitor therapy approaches $700 000 (€502 880).35 Likewise, statins in the absence of risk factors other than dyslipidaemia, are associated with an ICER per LYS as high as $195 000 (€140 088).36 Even less favourable ICERs relate to interventions that do not prolong survival or improve or even worsen quality of life. Such is the case for amiodarone which, compared with no therapy, is associated with an ICER per QALY of $1 239 600 (€890 529).37 Clearly, the cost effectiveness of some widely adopted drug therapies is much less favourable than that of ICD therapy.

Table 4

Cost-effectiveness data for various drug treatments and proceduresa

 ICERa
 
 US$ € Year of study 
Drug treatment    
Enalapril for heart failure 115/QALY 83 2002 
Intensive insulin therapy for a 25-year old 9614/QALY 6907 2002 
Carvedilol for heart failure 13 000/LYS 9339 1999 
Pravastatin in primary prevention 32 600/LYS 23 420 1997 
Treating hypertension to DBP <85 mmHg 86 360/LYS 62 041 1998 
ACEI for hypertension in echo-LVH 200 000/QALY 143 680 2003 
Screening at 50 years for proteinuria, then ACE 282 818/QALY 203 177 2003 
Warfarin for non-valvular AF in a 65-year-old 370 000/QALY 265 808 1995 
Treating hypertension to DBP <80 mmHg 658 370/LYS 472 973 1998 
ACEI for hypertension in unselected patients 700 000/QALY 502 880 2003 
Statin for primary prevention 54 000–1 400 000/QALY 38 793–1 005 760 2000 
Intensive insulin therapy for an 85-year-old 2 100 000/QALY 1 508 640 2002 
Procedures    
Primary PCI <30 000/QALY <21 552 1997 
Heart transplantation 28 000/LYS 20 115 2003 
Liver transplantation 26 000/LYS 18 678 2003 
Lung transplantation 77 000/LYS 55 317 2003 
 ICERa
 
 US$ € Year of study 
Drug treatment    
Enalapril for heart failure 115/QALY 83 2002 
Intensive insulin therapy for a 25-year old 9614/QALY 6907 2002 
Carvedilol for heart failure 13 000/LYS 9339 1999 
Pravastatin in primary prevention 32 600/LYS 23 420 1997 
Treating hypertension to DBP <85 mmHg 86 360/LYS 62 041 1998 
ACEI for hypertension in echo-LVH 200 000/QALY 143 680 2003 
Screening at 50 years for proteinuria, then ACE 282 818/QALY 203 177 2003 
Warfarin for non-valvular AF in a 65-year-old 370 000/QALY 265 808 1995 
Treating hypertension to DBP <80 mmHg 658 370/LYS 472 973 1998 
ACEI for hypertension in unselected patients 700 000/QALY 502 880 2003 
Statin for primary prevention 54 000–1 400 000/QALY 38 793–1 005 760 2000 
Intensive insulin therapy for an 85-year-old 2 100 000/QALY 1 508 640 2002 
Procedures    
Primary PCI <30 000/QALY <21 552 1997 
Heart transplantation 28 000/LYS 20 115 2003 
Liver transplantation 26 000/LYS 18 678 2003 
Lung transplantation 77 000/LYS 55 317 2003 

DBP, diastolic blood pressure, ACEI, angiotensin-converting enzyme inhibitors; echo-LVH, left ventricular hypertrophy according to echocardiography; PCI, percutaneous coronary intervention; Modified with permission from Leyva,34 with current exchange rate (1€=US$1.39 or C$1.42 or British £0.88).

aPresented as incremental cost-effectiveness ratio (ICER) per life year saved (LYS) or per quality-adjusted life year (QALY) saved. Cost in US$ and euros (€).

As for surgical operations, ICD therapy involves high up-front costs. In contrast, the cost of drug therapy is spread over the lifetime of the patient. In this respect, the 2007 NICE model38 revealed that lifelong drug therapy for a 50-year-old patient with heart failure (NYHA class III or IV) is £16 615 (€18 941). In this light, the ‘up-front’ cost of drug therapy is not dissimilar to that of ICD therapy. Similarly, ICD therapy appears less challenging when its cost is calculated on a daily rate (Table 5).30

Table 5

Cost of implantable cardioverter-defibrillator therapy on a daily rate

  Cost per day (€)*
 
Cost per day (€)a,b
 
 Cost of device+leads (€) At 5 years At 7 years At 5 years At 7 years 
Single-chamber ICD 11 800 6.10 4.20 7.80 5.40 
Dual-chamber ICD 13 500 7.00 4.80 9.00 6.20 
CRT-D device 15 000 7.80 5.40 9.90 6.90 
Weighted averagec 12 943 6.70 4.60 9.00 6.20 
  Cost per day (€)*
 
Cost per day (€)a,b
 
 Cost of device+leads (€) At 5 years At 7 years At 5 years At 7 years 
Single-chamber ICD 11 800 6.10 4.20 7.80 5.40 
Dual-chamber ICD 13 500 7.00 4.80 9.00 6.20 
CRT-D device 15 000 7.80 5.40 9.90 6.90 
Weighted averagec 12 943 6.70 4.60 9.00 6.20 

CRT-D, cardiac resynchronization therapy-defibrillation.

Costs per day to the nearest 10 cents.

aat 3% discounted rate.

b€1 = $1.28 dollars.

cWeighted for type of device implanted in the SEARCH-MI (Survey to Evaluate Arrhythmia Rate in so-Called High-risk Myocardial Infarction) registry.30 Modified with permission from Boriani et al.30

Conclusions

In any healthcare system, there is a delicate balance between what is good for the individual patient, what is good for society, and how much it all costs. As detailed above, most studies indicate that ICD therapy in appropriately selected patients at high risk of SCD is associated with cost-effectiveness ratios similar to, or better than, other accepted treatments, including renal dialysis. The up-front costs of ICD therapy are admittedly high and as such, ICD implantation is more akin to an operation than a drug. As would be the case for a life-saving operation, the adoption of short time horizons is apt to lead to underestimations of cost effectiveness. As well as the time horizon, the underlying aetiology of the arrhythmic substrate, implantation technique, ICD battery life, and the presence of co-morbidities are important issues in maximizing cost effectiveness. Above all, we should consider that ICD therapy is the only available option for prolonging survival in patients who are at risk of life-threatening ventricular arrhythmias. All value judgements made on with reference to cost-effectiveness analysis of ICD therapy must take this into consideration.

Funding

F.L. has received honoraria and research funding from Medtronic Inc., St Jude Medical and Sorin.

Conflict of interest: F.L. has received honoraria and research funding from Medtronic Inc, St Jude Medical, and Sorin. J.M.M. has received consulting fees and research support from St Jude Medical, Medtronic Inc., and Sorin.

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