This study quantifies the independent association of age on the length of survival following ICD implantation. Among all subjects >75 years at the time of ICD implantation, median survival was 5.3 years, about half that of the other two groups. After controlling for potential confounders and co-morbidities, age at ICD implantation remained strongly and significantly associated with subsequent total, cardiac, and non-cardiac mortality. Divergence in survival occurred early and continued to increase throughout the majority of follow-up time. While residual confounding could explain these results, most likely age itself does exert an effect on mortality independent of baseline co-morbidity status, via intrinsic effects of age on things such as risk of procedural complications and chance of future health events, items not controlled for by the baseline covariates included in our model. Given that age itself helps predict future longevity, a predictable but not previously consistent finding in past studies, we herein advocate for treating it as an additional co-morbidity to be considered when deeming appropriateness of ICD implantation.
These findings confirm and expand upon those reported by another single-centre retrospective study, which found a lower median survival after ICD implantation in octogenarians,20
and a Canadian study, which observed older age at ICD implantation to be associated with a higher risk of death.26
Our study included a longer follow-up period of comparisons across several age groups, and contained a more complete adjustment for confounding variables than was performed in either previous study. In particular, as the Canadian study aimed to identify the independent predictors of mortality, its authors pared down the covariates included in their final Cox model, rather than examining the association of age with mortality after fully adjusting for potential confounding factors. Additionally, our study showed that both cardiac and non-cardiac mortality risk increased with age.
In contrast to our results, several previous studies have shown comparable survival rates after ICD implantation in elderly and younger patient groups.21–23
Their elderly groups were younger (70 years or greater) when compared with those 75 years or greater in this study; of note is that in the present study, the 65- to 75-year-old group did display an increased risk of death when compared with those subjects <65 years of age. Two of these studies were performed outside the USA, where the patient selection process may be expected to be more stringent.21,23
The German study also had a significant difference between groups in the percent of subjects who received an ICD for secondary prevention and therefore were at lower risk of non-sudden cardiac death (78% of the elderly patient group vs. 63% of the younger group). The other two studies were small; the study by Geelen et al.
for example, included only 32 patient aged 70 years or greater. In the study by Quan et al.
the survival curves are seen to differentiate up to ~4 years, after which time no further deaths were observed among the older group. No denominators are given for the Kaplan–Meier curves, but by extrapolation their conclusion of similar mortality rates appears to be based on ~47 very robust elderly patients. Thus, healthier populations receiving ICDs, baseline demographic differences between age groups, and the small number of elderly patients in outside studies may all contribute to their finding of similar survival times between elderly and younger patients after ICD implantation.
Coincident with the survival benefit of ICD implantation among the elderly subset of MADIT-II, an increased mortality rate was seen in those ≥75 years when compared with those <75 years.16
In fact, while follow-up was insufficient to determine median survival, at 3.5 years, <60% of those highly selected elderly patients with ICDs were alive. As our median survival of 5.3 years among the elderly group echoes, ICD implantation may reduce mortality in the elderly, but it should be recognized to constitute a smaller absolute clinical benefit.
Our study results have potential implications for cost-effectiveness of ICDs in elderly patients. On the basis of data from eight large primary prevention trials, the incremental cost-effectiveness of prophylactic ICD therapy has been estimated to range from $34 000 to $70 200 per QALY added.9
Sensitivity analysis showed costs to remain less than $100 000 per QALY as long as mortality was reduced for ≥7 years, with estimated costs escalating quickly as the duration of efficacy was reduced, for example, to ~$50 000–$125 000 per QALY gained if ICD efficacy was assumed to cease after the first 5 years. Perhaps, more applicable to the current study, if the time horizon was simply truncated at 5 years cost estimates varied even more widely from $90 000 to $250 000. As all the patients in our study received an ICD, we cannot calculate risk reduction due to the ICD, but the absolute maximum average benefit in the elderly group is 5.3 years, and likely substantially shorter. Applying the estimates from Sanders et al.
to our elderly patient group, the estimated cost per QALY is at least $90 000 and likely much more. Though a single threshold for cost-effectiveness has not been established, values ranging from $50 000 to $120 000 per QALY have been proposed.27,28
Thus, among the patient population that we studied, ICD intervention among the elderly as a group may not be cost-effective. The large effect of the time horizon on estimates of cost-effectiveness supports careful consideration of age at the time of ICD implantation.
Our study has several limitations. This is a single-centre observational study and unidentified or residual confounding may be present. Additionally, we assessed and adjusted for only baseline co-morbidity status. While we hypothesize that age may exert some of its influence on mortality via predilection of those with increased age to have more health events, that is, progression of baseline co-morbidites and development of new diseases, it is beyond the scope of this study to address exactly how this may occur. Although the subjects comprising the study population were identified prospectively, the retrospective abstraction of the most of the data prohibited full resolution of all missing variables, which generally constituted 25% or less of the total population for any variable. Of note, we included in our models indicators for missing data status, and we did not find evidence of informative missingness. As cause of death was collected retrospectively, there may have been some error in differentiating primacy of cause, even crudely between cardiac and non-cardiac aetiologies, though any bias would likely be shared equally among groups. Further, the small number of non-cardiac deaths, particularly in the two younger age groups, should caution interpretation of these results. Primary prevention patients were represented only in the last few years of the study, concurrent with expanding indications for ICD implantation over the course of the study. Finally, as a cohort study of patients with defibrillators, we did not have a comparison group of elderly patients who did not receive ICDs.
In conclusion, in patients receiving ICDs, increased age is significantly and progressively associated with shorter survival times after ICD implant, after controlling for known confounders. As the co-morbidity burden of this population can have a meaningful impact on survival, we would advocate an individualized approach. We would not recommend a strict age cutoff for ICDs, but perhaps a recommendation to limit their application to those expected to live more than 5 years after implantation. Age and co-morbidities should be addressed in estimating the time horizon for the effectiveness of ICDs in future cost-effectiveness analyses.