Rome, Italy - New trials of prophylactic implantable cardioverter defibrillator (ICD) therapy in seniors are needed, because the seminal studies of ICDs in heart-failure patients do not show a survival benefit in older patients, the authors of a new meta-analysis argue.
Dr. Pasquale Santangelli (Catholic University of the Sacred Heart, Rome, Italy) and colleagues searched the literature for randomized, controlled trials of prophylactic ICD vs medical therapy in patients with severe left ventricular dysfunction that reported data about mortality outcomes for different age groups. They identified five trials, MADIT-II, DEFINITE, DINAMIT, SCD-HeFT, and IRIS, enrolling 5783 patients, of whom 44% were over 60 years old. The results of their meta-analysis are published in the November 2, 2010 issue of the Annals of Internal Medicine.
Their primary analysis included MADIT II, DEFINITE, and SCD-HeFT, because those studies reflected the most common approach to prophylactic ICD therapy in heart-failure patients, according to the authors. The pooled analysis of those three trials confirmed the overall findings of the individual trials—that prophylactic ICD therapy reduces mortality in younger patients (HR 0.65, p<0.001), but the survival benefit in older patients was smaller and statistically nonsignificant (HR 0.81, p=0.11). A second meta-analysis that also included DINAMIT and IRIS, which enrolled patients early after MI, showed similar results.
The authors conducted the meta-analysis because recent epidemiological studies have reported that elderly patients with severe left ventricular dysfunction have reduced life expectancy, usually due to nonarrhythmic causes, according to Santangelli.. Also, elderly patients are underrepresented in primary-prevention ICD trials, so the evidence that they benefit as much from ICD therapy as younger patients do is so far from conclusive.
"We believe that there are cogent arguments supporting the necessity of an appropriately designed primary-prevention ICD trial focused on elderly patients," Santangelli said. "This [would show results] independent of the results of any subgroup analysis of published studies and also independent of the results of our meta-analysis, [because] none of the published primary-prevention ICD trials were powered to definitely answer the crucial question of the benefit of prophylactic ICD therapy in the elderly, and our meta-analysis, which included data from subgroup analyses of primary-prevention trials, led to inconclusive results."
"Only an appropriately designed randomized trial of prophylactic ICD in the elderly would give a definite answer to this important question," he said. Because of the significant rate of nonarrhythmic heart-failure mortality in elderly patients with severe left ventricular dysfunction, this proposed trial should compare optimal medical therapy plus cardiac resynchronization therapy, optimal medical therapy plus ICD, and optimal medical therapy alone in elderly patients with severe left ventricular dysfunction, Santangelli said. Because of the overall increase in life expectancy of the population and the emergence of medical therapies that were not always used in the older ICD trials, he suggests that future studies focused on ICD therapy in older patients use 75 as the cutoff between "older" and "younger" patients.
In the meantime, "it would be improper to withhold ICD therapy in the elderly based on our findings, since only an appropriately designed randomized trial of prophylactic ICD in the elderly would give a definite answer to this important question," he said.
Santangeli P, Di Biase L, Dello Russo A, et al. Meta-analysis: age and effectiveness of prophylactic implantable cardioverter-defibrillators. Ann Intern Med 2010; 153:592-599.