BOSTON – More than a decade’s worth of follow-up of participants in the SCD-HeFT trial confirms that implantable cardioverter defibrillators in patients with moderate heart failure and reduced left ventricular systolic function can significantly reduce mortality, Dr. Jeanne Poole reported at the annual meeting of the Heart Rhythm Society.
ICD therapy was most beneficial in patients with New York Heart Association (NYHA) class II disease and ischemic heart failure, reported Dr. Poole, professor of medicine and director of the arrhythmia service and electrophysiology laboratory at the University of Washington in Seattle.
But as the original analysis of SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) showed, ICDs did not appear to benefit patients with NYHA class III disease, for whom cardiac resynchronization therapy (CRT) was not available at the time of enrollment (N. Engl. J. Med. 2005;352:225-37). Additionally, ICDs benefited patients with ischemic, but not nonischemic, heart failure, Dr. Poole noted.
Despite the significant reduction in mortality seen in some patients, "the mortality we observed at median follow-up of 11 years is substantial and reflects the reality of patients diagnosed at least a decade ago with heart failure," she said at a late-breaking abstracts session.
The SCD-HeFT trial was designed to see whether amiodarone (Cordarone, Pacerone) or a single-lead ICD, programmed conservatively to shock only, could reduce all-cause mortality compared with placebo in patients with ischemic or nonischemic NYHA class II-III heart failure with ejection fraction 35% or less.
In all, 829 patients were assigned to receive ICDs, 845 to amiodarone, and 847 to placebo during 1997-2001. The trial ended in October 2003.
An intention-to-treat analysis at 5 years (median follow-up 45.5 months) showed that although amiodarone was no better than placebo at preventing deaths, ICD treatment was associated with a 7.2% absolute risk reduction (hazard ratio, 0.77; P = .007).
The current analysis carried follow-up out an additional 5 or more years. The investigators contacted the 148 original trial enrollment sites asking for data on the patients. Two of the sites reported that all of the patients enrolled there had died, 110 others provided mortality data (89 included clinical or arrhythmia data), and 36 sites did not respond or chose not to participate.
Mortality data were available for 2,294 of the original 2,521 participants (91%).
The 12-year all-cause mortality for patients randomized to ICD treatment was 59%, compared with 64% for patients randomized to placebo (HR, 0.87; P = .028), translating into an absolute risk reduction of 5%.
Among patients with NYHA class II heart failure at enrollment, the all-cause mortality rate was significantly lower than among patients originally assigned to placebo (HR, 0.76; P = .001). However, patients with class III disease at enrollment did no better than did controls (HR, 1.06).
Similarly, patients with an ischemic heart failure etiology did better than did placebo patients (HR, 0.81; P = .001), but those with nonischemic origin did not.
Consistent with the observations in the original trial, amiodarone did not confer a survival benefit compared with placebo.
Study limitations include vital status determination on only 91% of the original participants, limited data on new ICD implants during follow-up, and limited data on long-term use of amiodarone. Additionally, "long-term mortality for patients in the original randomized treatment groups may have been confounded by multiple clinical and advanced heart failure therapies after SCD-HeFT was completed," Dr. Poole noted.
Dr. Christine M. Albert, director of the center for arrhythmia prevention at Brigham and Women’s Hospital in Boston, said in an interview that the long-term data show that clinicians need better tools than just ejection fraction for determining which patients with heart failure are most at risk and could benefit from more aggressive interventions.
"SCD-HeFT showed a 5% absolute difference. It would be nice to find a group of indicators that would tell you who is really going to be at risk for arrhythmic death but live 10 years with their heart failure. Unfortunately, because they don’t have the updated information about therapy, it’s difficult to make a lot of interpretation of their results," she said.
Dr. Albert comoderated the session in which the data were presented, but was not involved in the study.
The study was funded by the National Heart, Lung, and Blood Institute with a subsidiary grant for St. Jude Medical Corp., maker of the ICD used in the study. Dr. Poole disclosed being on the speakers bureau for St. Jude Medical, Medtronic Inc., and Boston Scientific Corp. Dr. Albert disclosed receiving research support from St. Jude Medical.