Researchers comparing patients who received implantable cardioverter-defibrillators (ICDs) in clinical trials and patients in an ICD registry found no significant differences in survival rates between the two groups, but ICD patients had significantly improved survival rates over those patients in clinical trials who received medical treatment only. The Journal of the American Medical Association published these findings Jan. 2.
According to lead author Sana M. Al-Khatib, MD, of Duke Clinical Research Institute in Durham, N.C., and colleagues, results in clinical practice often do not mirror the results of clinical trials. Clinical trial populations typically exhibit fewer comorbidities, receive closer monitoring and are treated by more experienced physicians than the general patient population, and these factors may account for the discrepancies in outcomes. Al-Khatib et al compared trial populations with a matched registry population to determine whether the enhanced survival rates in trials of ICDs were evident in the general patient population of ICD recipients.
The researchers used original patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II, 1,232 patients) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT, 1,676 patients randomized to receive placebo or ICD therapy). MADIT-II found that after a mean 20-month follow-up, patients receiving ICD therapy had reduced mortality compared with patients who received medical therapy (14.2 percent vs. 19.8 percent). SCD-HeFT also found reduced mortality among ICD patients compared with a population that received placebo and amiodarone after a mean follow-up of 45.5 months (22 percent vs. 29 percent).
Al-Khatib et al used data from the National Cardiovascular Disease ICD Registry to select the comparison population. They queried the registry for patients who were enrolled between Jan. 1, 2006, and Dec. 31, 2007, and with the same clinical characteristics as the patients enrolled in the MADIT-II and SCD-HeFT trials (trial-eligible group). The researchers found significant differences in baseline clinical variables between the trial groups and the trial-eligible groups, so they conducted propensity score matching to assure a comparison of similar patients. After propensity scoring they selected a cohort of registry patients matched to each trial participant in a 2:1 registry-to-trial ratio. The endpoint of the study was all-cause mortality.
The researchers found no significant differences in the two-year mortality rates of MADIT-II patients who received ICD therapy (15.6 percent) and MADIT-like patients (13.9 percent). The two-year mortality rate of MADIT-like patients was significantly better than that of patients randomized to medical therapy in the MADIT-II trial (13.9 percent vs. 22 percent). Comparisons of three-year mortality of SCD-HeFT patients randomized to receive ICD with SCD-HeFT-like patients from the registry yielded almost identical rates (17.3 percent vs. 17.4 percent). Survival of the SCD-HeFT-like patients was significantly better than the survival of trial patients who received placebo (17.3 percent three-year mortality vs. 22.4 percent).
When the researchers studied subgroups of patients 65 years of age and older, they again found no significant differences in the survival rates of patients who received ICDs in clinical trials and those who were trial-eligible (MADIT II patients 19.8 percent vs. 16.5 percent for MADIT–like patients; SCD-HeFT patients 24.8 percent vs. 21.8 percent for SCD-HeFT-like patients). The trial-eligible patients had significantly better rates of survival than trial participants who received medical treatment only or placebo (MADIT-like patients 16.5 percent vs. 31.5 percent for MADIT II patients randomized to medical treatment; SCD-HeFT-like patients 21.8 percent vs. 30.2 percent for SCD-HeFT patients receiving placebo).
The researchers concluded that the positive effect of ICD implantation on morbidity demonstrated in clinical trials was generalizable to the patients who receive ICDs in routine clinical practice, even in the subset of older patients. “These findings underscore the effectiveness of primary prevention ICD therapy in clinical practice,” they wrote.
The registry patients who comprised the study-eligible cohort may not be reflective of the general patient population that receives primary prevention ICDs, and the researchers noted this fact as a limitation of their study. Other limitations were an inability to capture clinical data not recorded in the registry, dependence on the accuracy of clinical records and the short follow-up periods of the trials.