Impact of Age and Medical Comorbidity on the Effectiveness of Implantable Cardioverter-Defibrillators for Primary Prevention

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Although implantable cardioverter-defibrillators (ICDs) reduce mortality in primary prevention patients with left ventricular systolic dysfunction, recent studies have questioned their overall role in clinical practice, especially in older patients and those with major comorbid conditions. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> In a prospective cohort of 965 patients with ischemic and nonischemic cardiomyopathies (ejection fraction ≤35%) and no prior ventricular arrhythmias, we compared long-term mortality in patients who did (n=494 [51%]) and did not receive ICDs over a mean follow-up period of 34�16 months. Using a landmark analysis, multivariable Cox proportional hazards models that included propensity scores for ICD implantation assessed the relationship between ICD therapy and mortality in the entire cohort and by age and the presence of major comorbid conditions. Data from these analyses were then used as inputs in a Markov model to generate incremental cost-effectiveness ratios for ICD therapy. Patients who received ICDs were similar in age and prevalence of most major comorbid conditions, including symptomatic heart failure. After multivariable adjustment, ICD therapy was associated with a 31% lower risk for all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.50 to 0.96; <jats:italic>P</jats:italic> =0.03). The relationship between ICD therapy and lower all-cause mortality was consistent after stratification by age (<65, 65 to 74, and ≥75), ischemic etiology, ejection fraction (>25% versus ≤25%), and the presence of major comorbid conditions (probability values for all interactions >0.05). Incremental cost-effectiveness ratios for ICD therapy were similar between patients aged ≥75 years and younger patients but rose slightly in those with multiple comorbid conditions. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Routine use of ICDs in primary prevention patients with left ventricular systolic dysfunction was associated with lower all-cause mortality, even among older patients and those with major comorbid conditions. Although their use needs to be individualized, our findings suggest that these groups should not be routinely excluded from ICD treatment. </jats:p>