European Heart Journal

European Heart Journal Advance Access originally published online on February 5, 2007
European Heart Journal 2007 28(14):1746-1749; doi:10.1093/eurheartj/ehl438

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Role of the implantable defibrillator among elderly patients with a history of life-threatening ventricular arrhythmias

Jeffrey S. Healey^1,*, Al P. Hallstrom², Karl-Heinz Kuck³, Girish Nair¹, Eleanor P. Schron⁴, Robin S. Roberts⁵, Carlos A. Morillo¹ and Stuart J. Connolly¹

¹ Population Health Research Institute, Hamilton Health Sciences—General Site, McMaster University, 237 Barton St. E amilton, Ontario, Hamilton, Canada L8L 2X2
² Department of Biostatistics, University of Washington, Seattle, Washington, USA
³ Allgemeines Krankenhaus, St. Georg, Hamburg, Germany
⁴ National Heart, Lung and Blood Institute, Bethesda, Maryland, USA
⁵ Henderson Research Group, McMaster University, Hamilton, Canada

Received 6 July 2006; revised 11 October 2006; accepted 24 November 2006; online publish-ahead-of-print 5 February 2007.

^* Corresponding author. Tel: +1 905 577 8004; fax: +1 905 521 8820.E-mail address: healey{at}hhsc.ca

See page 1665 for the editorial comment on this article (doi:10.1093/eurheartj/ehl549)

	Abstract

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Aims: The implantable defibrillator (ICD) reduces arrhythmic and all-cause mortality in patients with a history of life-threatening ventricular arrhythmias. However, its effectiveness in elderly patients is uncertain, given their competing risk of non-arrhythmic death.

Methods and results: Individual patient data from all three secondary prevention trials comparing the ICD to amiodarone were pooled. Patients were divided into two groups based on age < 75 and 75 years. Patient characteristics were reported and the effect of the ICD on all-cause mortality and arrhythmic death was determined for each group. The effect of age on these outcomes was determined by evaluating the interaction term (age-treatment). A total of 1866 patients were included in this analysis. Their mean age was 63.7 ± 10.4 years (intra-quartile range 58–71 years). There were 252 patients 75 years old (13.5% of total). Patients 75 years old had a similar left ventricular (LV) ejection fraction (EF)(32.6 ± 13.7 vs. 33.8 ± 14.9%, P = 0.20) and baseline prevalence of NYHA class 3 or 4 heart (12.3 vs. 11.8%, P = 0.38) failure as younger patients, but were less likely to have ventricular fibrillation as their presenting arrhythmia (39 vs. 53%, P = 0.0001). Over a mean follow-up of 2.3 years, older patients were more likely to die of non-arrhythmic death (8.74% per year vs. 3.96% per year, P = 0.001) and arrhythmic death (6.73% per year vs. 3.84% per year, P = 0.03). The ICD significantly reduced all-cause and arrhythmic death in patients < 75 years old (all-cause death HR = 0.69, 95% CI: 0.56–0.85, P < 0.0001; arrhythmic death HR = 0.44, 95% CI: 0.32–0.62, P < 0.0001), but not in patients 75 years old (all-cause death HR = 1.06, 95% CI: 0.69–1.64, P = 0.79; arrhythmic death HR = 0.90, 95% CI: 0.42–1.95, P = 0.79). The interaction between age 75 and ICD use was of borderline significance in each case (P = 0.09 and P = 0.11, respectively).

Conclusion: Elderly patients with a history of life-threatening ventricular arrhythmias have a high incidence of non-arrhythmic death. In these patients, the ICD may not afford the same survival advantage over amiodarone that is seen in younger patients. ICD therapy should not be withheld based on age alone; however, physicians should carefully consider the risk of non-arrhythmic death among elderly patients when selecting the appropriate therapy for an individual.

Key Words: Implantable defibrillator • Ventricular tachycardia • Cardiac arrest • Mortality • Elderly

	Introduction

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Three randomized trials have compared the implantable defibrillator (ICD) to anti-arrhythmic medication for the treatment of patients with life-threatening ventricular arrhythmias.^1–3 Together, they demonstrate a 28% reduction in all-cause mortality among patients receiving an ICD, when compared with amiodarone (95% CI: 0.60–0.87, P = 0.0006), which is primarily due to a 50% reduction in arrhythmic death (95% CI: 0.37–0.67, P < 0.0001).⁴ However, this benefit was not observed in all patient sub-groups. A pooled analysis of all three trials did not find a survival benefit from the ICD in patients with a left ventricular (LV) EF of > 35%.⁴ Given the cost⁵ and potential complications¹ of these devices, it is desirable to identify patients who are most likely to benefit.

Although none of the ICD trials excluded elderly patients,^1–3 elderly patients were poorly represented in these trials, which all had a mean age of participants of < 70 years.^1–3 Therefore, the overall results of these trials may not be applicable to an elderly population. The ICD reduces only arrhythmic death, thus its ability to reduce all-cause mortality depends on a relatively high frequency of arrhythmic death in the population treated. It also depends on a relatively low rate of non-arrhythmic death. The ratio of sudden death to all-cause death has been shown to fall steadily from 0.51 before age 50 to 0.26 after age 80,⁶ in patients with heart failure or following myocardial infarction. Thus, one would expect that elderly survivors of cardiac arrest may benefit less from the ICD than younger patients. This analysis was conducted to determine the effect of age on the benefits of the ICD in survivors of cardiac arrest.

	Methods

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The methods used to collect and combine the patient-level data from the three secondary prevention defibrillator trials^1–3 have been previously described in detail.⁴ Patient-level data from the Anti-Arrhythmics vs. Implantable Defibrillators (AVID),² Cardiac Arrest Study—Hamburg (CASH)³, and Canadian Implantable Defibrillator Study (CIDS)¹ trials, for patients randomized to either an ICD or amiodarone, were collated into a master database, using pre-defined operational definitions for patient characteristics and outcomes.⁴ Using the pooled dataset, age 75 years was prospectively defined as representing elderly, prior to any age-specific data analyses. Patient characteristics were described for these two age groups, and survival curves constructed for all-cause mortality and arrhythmic death. Categorical variables were compared using Fisher's exact test. The effect of the ICD on all-cause and arrhythmic mortality was expressed using the hazard ratio. Heterogeneity between trials for these outcomes was evaluated using the chi-squared test. The influence of age 75 on the size of the ICD treatment effect was evaluated using Cox proportional hazard modelling by determining the significance of the interaction term, when added to a model including both treatment allocation and age group and including data on both age groups. The suitability of the Cox model was assessed graphically and all analyses were stratified by the study of origin. Sensitivity analyses were conducted using different age cut-offs to define the elderly and the effect of age as a continuous variable was also evaluated. Throughout, a two-sided P-value of < 0.05 was considered statistically significant; however, P-values were not adjusted for multiple comparisons.

	Results

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This analysis included a total of 1866 patients, who were randomized to receive an ICD or amiodarone. The mean age was 63.7 ± 10.4 years (intra-quartile range 58–71). There were 252 patients (13.5% of total) 75 years old. The AVID trial had a higher percentage of patients 75 years old than either the CIDS or CASH trials (18.1 vs. 9.4 vs. 3.1%, P = 0.0001) There were no significant differences in LV ejection fraction (EF), heart failure severity, history of myocardial infarction, or prior coronary bypass between the two age groups (Table 1). However; older patients were more likely to present with syncopal ventricular tachycardia and less likely to present with ventricular fibrillation (Table 1).

View this table: [in this window] [in a new window]   Table 1 Baseline characteristics in patients: age < 75 years vs. 75 years

 
In patients < 75 years old, the ICD significantly reduced both all-cause (HR = 0.69, 95% CI: 0.56–0.85, P < 0.0001) and arrhythmic death (HR = 0.44, 95% CI: 0.32–0.62, P < 0.0001) (Figure 1A and C). Neither benefit was clearly observed in the group of patients 75 years old (HR = 1.06, 95% CI: 0.69–1.64, P = 0.79, and HR = 0.90, 95% CI: 0.42–1.95, P = 0.79, respectively) (Figure 1B and D). Cox proportional hazard modelling demonstrated a borderline-significant interaction between age 75, and the effect of the ICD on both all-cause (P for interaction = 0.09) and arrhythmic death (P for interaction = 0.11). There was no significant heterogeneity between the individual trials for either all-cause mortality (P = 0.31) or arrhythmic death (P = 0.17).

View larger version (27K): [in this window] [in a new window] [Download PowerPoint slide]   Figure 1 Overall survival and freedom from arrhythmic death in patients under 75 years of age (A, C), and 75 years or older (B, D).

 
Over a mean follow-up of 2.3 ± 1.9 years, the incidence of death from heart failure or non-cardiac causes was significantly higher among patients 75 years old; however, the rate of arrhythmic death was similar between the two groups (Table 2). This gives a ratio of arrhythmic death to all-cause mortality that is lower in patients 75 years old (Table 2). Within the first year after randomization, these differences in cause-specific mortality were even more significant, as elderly patients were more likely to die of non-cardiac causes (4.4 vs. 1.2%, P = 0.001) and heart failure (9.1 vs. 4.3%, P = 0.002), but not arrhythmic death (6.0 vs. 4.9%, P = 0.44).

View this table: [in this window] [in a new window]   Table 2 Cause-specific mortality rates (% per year)

 
Sensitivity analyses were conducted, to explore the effect of age on arrhythmic and all-cause mortality. As one lowers the age cut-off that defines elderly, a greater reduction in arrhythmic and all-cause mortality is seen with the ICD, in the older age group. There is a statistically significant improvement in survival with the ICD among the elderly age group using a cut-off of > 70 years old for all-cause mortality and > 72 years old for arrhythmic mortality. If one examines age as a continuous variable, age does not influence the effect of the ICD on all-cause mortality (P = 0.38) or arrhythmic death (P = 0.71).

	Discussion

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Based on the pooled results of all secondary prevention ICD trials, there is a suggestion that elderly patients may derive less benefit from an ICD than younger patients, although this effect is not nominally statistically significant. The biological plausibility of this observation is supported by the marked increased incidence of non-arrhythmic mortality among elderly patients, often occurring during the first year after their ventricular arrhythmia. The increase in non-arrhythmic death in the elderly is due to an increase in both non-cardiac and heart failure mortality, and is consistent with prior observational reports indicating a lower proportional risk of arrhythmic death among the elderly.⁶ In fact, the rate of non-cardiac mortality in this pooled analysis almost certainly underestimates the true rate, as patients with serious non-cardiac conditions were excluded from participating in these trials.¹

Several cohort studies have previously examined outcomes in elderly ICD recipients. The first report examined 769 patients, including 74 patients 75 years, who received an ICD between 1983 and 1995, a period spanning the introduction of trans-venous systems.⁷ The investigators found an increased 4 year mortality among elderly recipients (43 vs. 22%, P = 0.0001), which was due to an increased rate of non-arrhythmic, cardiac death.⁷ Elderly patients had similar rates of appropriate shocks (42 vs. 43% at 4 years) compared to younger patients; despite the fact that 43% of elderly patients had an epicardial implant, only 1 elderly patient died within the peri-operative period. This latter observation is consistent with the observation that elderly recipients of pacemakers and ICDs have similar complication rates as younger patients,⁸ except perhaps a slightly increased risk of lead perforation.⁹ In a more recent cohort study, 102 patients 70 years old, who received an ICD between 1999 and 2003, were compared to 273 younger patients.¹⁰ Over a mean follow-up of 26.5 ± 18.1 months, the investigators found similar mortality between groups (12.7 vs. 12.5%), and similar rates of appropriate shocks (44 vs. 40%).¹⁰ The more favourable outcomes among elderly patients in this later report may, as the authors suggest,¹⁰ reflect advances in the medical therapy of heart failure or may simply result from the lower age cut-off used to define the elderly. Three additional cohort studies, which included nearly 200 patients over the age of 75, also suggest equivalent survival among elderly ICD recipients;^11–13 however, each of these cohort studies is small and susceptible to selection bias, as only ‘healthier’ elderly patients may have received ICDs.

The optimal treatment of elderly survivors of life-threatening ventricular arrhythmias must include careful consideration of their co-morbidities and the patients’ goals of therapy.^14,15 For patients with co-morbidities, such as advanced heart failure, life-prolonging therapy with an ICD, may be less attractive than other therapies, such as cardiac resynchronization,¹⁶ that may also improve quality of life.¹⁴ Overall, in the present analysis, almost 20% of elderly patients died within 1 year of their episode of life-threatening ventricular arrhythmia, and three-quarters of these deaths were due to non-arrhythmic causes. Accordingly, particular attention needs to be given to the risk of non-arrhythmic death in the elderly when deciding on the optimal therapy for their arrhythmia.

Limitations of current analysis
The apparent reduction in the effectiveness of the ICD among elderly patients must be interpreted cautiously as there were only 252 elderly patients in this analysis, and thus limited statistical power to detect an interaction between age 75 years and the effectiveness of the ICD. As well, age 75 years was just one of many sub-groups analysed using this data-set, thus it should be appreciated that the results of this analysis are more susceptible to type-I error. Still, this analysis includes more elderly patients than the two large cohort studies combined,^7,10 includes every elderly patient from all secondary prevention ICD trials, and is a randomized evaluation of the ICD in elderly patients. As a randomized controlled trial is the only proper way to address this question and further randomized trials in secondary prevention are unlikely, we are left to make important decisions based on this analysis and the results of cohort studies. Although the results of this analysis are not compelling enough to conclude that ICDs do not benefit elderly patients, they should be cause for caution. The excess of non-arrhythmic deaths among elderly patients in this study is clear, consistent with previous reports,^6,7 and provides biological plausibility for a reduced effectiveness of ICDs in the elderly.⁷

The results of this analysis do not apply to the use of the ICD as primary prophylaxis against arrhythmic death. There is a greater opportunity for patient selection and referral bias in primary prevention, thus elderly patients referred for primary prophylaxis may be more likely to benefit from an ICD than elderly survivors of life-threatening ventricular arrhythmias.¹⁷ Indeed, patients from the MADIT-II trial, who where 75 years old (n = 204), experienced a 46% relative risk reduction in total mortality when randomized to receive an ICD (P = 0.04).¹⁸ However, sub-group analyses from the COMPANION¹⁹ and SCD-HeFT²⁰ trials suggest a trend (statistically non-significant) towards a reduced benefit of the ICD in patients older than 65 years; perhaps a reflection of the increased prevalence of heart failure in these two trials.

Progressive heart failure was the major cause of death among elderly patients in this analysis. ICDs that incorporate biventricular pacing reduce heart failure mortality^16,19 in patients with severe LV dysfunction and a prolonged QRS duration, and the appropriate use of these devices could result in a more favourable impact on overall mortality in elderly patients.

	Conclusions

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Elderly patients with a history of life-threatening ventricular arrhythmias have a high incidence of non-arrhythmic death. In these patients, the ICD may not afford the same survival advantage over amiodarone that is seen in younger patients. ICD therapy should not be withheld based on age alone; however, physicians should carefully consider the risk of non-arrhythmic death among elderly patients when selecting the appropriate therapy for an individual.

Conflict of interest: J. S. H. is the recipient of a personnel grant from the Canadian Institutes of Health Research. The authors declare no conflicts.

	References

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1. Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, Mitchell LB, Green MS, Klein GJ, O'Brien B. Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation (2000) 101:1297–1302.[Abstract/Free Full Text]
2. The Antiarrhythmics versus implantable defibrillators (AVID) investigators. A comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med (1997) 337:1576–1583.[Abstract/Free Full Text]
3. Kuck KH, Cappato R, Siebels J, Ruppel R. A randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg. Circulation (2000) 102:748–754.[Abstract/Free Full Text]
4. Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, Greene HL, Boczor S, Domanski M, Follmann D, Gent M, Roberts RS. Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. Eur Heart J (2000) 21:2071–2078.[Abstract/Free Full Text]
5. O'Brien BJ, Connolly SJ, Goeree R, Healey JS, Roberts RS, Gent M, Connolly SJ. Cost-effectiveness of the implantable cardioverter-defibrillator: Results from the Canadian Implantable Defibrillator Study (CIDS). Circulation (2001) 103:1416–1421.[Abstract/Free Full Text]
6. Krahn A, Connolly SJ, Roberts RS, Gent M, ATMA Investigators. Diminishing proportional risk of sudden death with advancing age: implications for prevention of sudden death. Am Heart J (2004) 147:837–840.[CrossRef][Web of Science][Medline]
7. Panotopoulos PT, Axtell K, Anderson AJ, Sra J, Blanck Z, Deshpande S, Biehl M, Keelan ET, Jazayeri MR, Akhtar M, Dhala A. Efficacy of the implantable cardioverter-defibrillator in the elderly. J Am Coll Cardiol (1997) 29:556–560.[Abstract]
8. Bailey SM, Wilkoff B. Complications of pacemakers and defibrillators in the elderly. AJGC (2006) 15:102–107.
9. Mahapatra S, Bybee KA, Bunch TJ, Espinosa RE, Sinak LJ, McGoon MD, Hayes DL. Incidence and predictors of cardiac perforation after permanent pacemaker placement. Heart Rhythm (2005) 2:907–911.[CrossRef][Web of Science][Medline]
10. Duray G, Richter S, Manegold J, Israel CW, Gronefeld G, Hohnloser SH. Efficacy and safety of ICD therapy in a population of elderly patients treated with optimal background medication. J Interv Card Electrophysiol (2005) 14:169–173.[CrossRef][Web of Science][Medline]
11. Noseworthy PA, Lashevsky I, Dorian P, Greene M, Cvitkovic S, Newman D. Feasibility of implantable cardioverter-defibrillator use in elderly patients. A case series of octogenarians. PACE (2004) 27:373–378.[Medline]
12. Farooq M, Staniforth AD, Early MJ. Outcome after implantable cardioverter defibrillators (ICD) in the elderly. Presented at the Heart Rhythm Society 25 th Anuual Scientific Sessions, May 19–24, 2004: San Francisco, California.
13. Kleman JM, Pinski SL, Morant VA. ICDs in the very elderly: Short and long-term outcome. PACE (1994) 17:835.
14. Lewis EF, Johnson PA, Johnson W, Collins C, Griffin L, Stevenson LW. Preferences for quality of life or survival expressed by patients with heart failure. J Heart Lung Transplant (2001) 20:1016–1024.[CrossRef][Web of Science][Medline]
15. Traub D, Ganz L. Implantable cardioverter-defibrillators for secondary prevention: is it worth it in the elderly? AJGC (2006) 15:93–99.
16. Cleland JG, Daubert J-C, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure (CARE-HF) study Investigators. The effect of cardiac resynchronization on morbidity and mortalilty in heart failure. N Engl J Med (2005) 352:1539–1549.[Abstract/Free Full Text]
17. Daubert JP, Sesselberg HW, Huang DT. Implantable cardioverter-defibrillators for primary prevention: How do the data pertain to the aged? AJGC (2006) 15:88–92.
18. Huang DT, Sesselberg HW, Salam T, Daubert JP, Rosero SZ, Andrews M, Hall WJ, Zareba W, Moss AJ. Survival benefits associated with defibrillator implant in the elderly patients enrolled in MADIT II. Circulation (2003) 108(Suppl. 17):1790.[Free Full Text]
19. Bristow MR, Saxon LA, Boehmer J, Kruger S, Kass D, DeMarco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced heart failure. N Engl J Med (2004) 347:2140–2150.
20. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med (2005) 352:225–237.[Abstract/Free Full Text]

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