The May 20th issue of the New England Journal of Medicine featured two articles that continue to feed the dialogue regarding devices and heart failure. The results of the COMPANION study and the DEFINITE study were both published, and a review of these studies and implications for practice follows.

       The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) study enrolled a total of 1,520 patients with New York Heart Association (NYHA) heart failure classifications III or IV, having ischemic or nonischemic cardiomyopathies, with a QRS width of at least 120 msec and an ejection fraction (EF) of 0.35 or less. The study hypothesis asked the question of whether prophylactic cardiac-resynchronization therapy with pacemaker or with pacemaker and ICD would reduce the risk of death and rate of hospitalization in patients with advanced heart failure. Subjects in this multicenter trial were randomized in a 1:2:2 fashion to optimal drug therapy, drug therapy plus resynchronization, or drug therapy plus resynchronization plus ICD.
       The optimal pharmacologic therapy as defined in this study included use of diuretics, angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers, beta-blockers and spironolactone. Use of other medications was at the physician’s discretion. The group randomized to cardiac resynchronization therapy received the Contak TR model 1241 pacemaker by Guidant, and those receiving the pacemaker-defibrillator combination had the Contak CD model 1823 by Guidant implanted. Study endpoints were: 1) primary endpoint: a composite of death from any cause or hospitalization for any cause; and 2) secondary endpoint: death from any cause.
       The results of this study follow. Cardiac-resynchronization therapy and resynchronization therapy with ICD both decreased the risk of death or hospitalization more than the use of drugs alone. There was a 34% reduction in the pacemaker group and 40% reduction in the pacing-ICD group, compared to the drug-only group. For the death from any cause endpoint, pacing reduced incidence by 24% and the pacemaker defibrillator reduced risk by 36%. Thus, for this patient population, cardiac-resynchronization therapy alone decreased mortality significantly and in combination with ICD did so even further. It was concluded that resynchronization, and further, resynchronization with ICD significantly reduces mortality in patients with advanced heart failure. These results are summarized in Table 1.

Tables 1 and 2.

COMPANION and DEFINITE trials.

       The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial hypothesized that ICD therapy would reduce the risk of death in patients with nonischemic cardiomyopathy and moderate-to-severe left ventricular dysfunction. This was a multi-center study in which patients were randomized 1:1 to optimal medical therapy versus optimal medical therapy plus ICD (single chamber St. Jude Medical ICD). The population (which ultimately consisted of 458 patients), qualified for the study by having documented LVEF of < 36%, symptomatic heart failure (NYHA Class IV excluded), nonischemic dilated cardiomyopathy, and evidence of ambient arrhythmias (defined as a recorded episode of NSVT or at least 10 PVCs per hour on a 24-hour Holter). Primary endpoint for this study was death from any cause; secondary endpoint was sudden death from arrhythmia.
       The DEFINITE trial results follow. For primary endpoint, fewer patients died in the ICD group (28 versus 40) but the difference was not considered significant. For the secondary endpoint, arrhythmic death, it was found that there were three deaths in the ICD group and 14 in the standard therapy group, which was considered significant. The results are summarized in Table 2.
       The populations of these studies were quite different (Tables 1 and 2). The COMPANION patients were a mix of ischemic and nonischemic patients, while DEFINITE enrolled only nonischemic patients. COMPANION patients were older, had more severe NYHA classifications, were more likely to have diabetes, did worse on the six-minute walk test, and were more likely to have bundle branch blocks. The average ejection fraction for the two groups was comparable, at 22% and 21.4%. The patients in DEFINITE were also different in that they had to demonstrate ambient arrhythmias for study qualification.
       These two studies have contributed further evidence of the benefit of device therapy for heart failure patients. This data, added to that from prior studies, helps to further refine the criteria for identification of those who may qualify for what is many times a life-saving option.