Related Resources • Review of cardiomyopathy and heart failure • Links related to heart failure

By DrRich

Dateline: November 25, 2002

On November 21, COMPANION, a major clinical trial evaluating cardiac resychronization therapy (CRT) in patients with heart failure (click here for a quick review of heart failure), was abruptly halted by the Data Safety and Monitoring Board.  The study was stopped when the study data being accumulated was found to show a major and significant survival benefit to the patients with heart failure who had been randomized to receive CRT.

CRT (sometimes called biventricular pacing) uses a specialized pacemaker to re-coordinate the action of the right and left ventricles in patients with heart failure. (Click here for a quick review of the heart's anatomy.) In approximately 30% of patients with heart failure, an abnormality in the heart's electrical conducting system (called an "intraventricular conduction delay" or bundle branch block) causes the two ventricles to beat in a asynchronous fashion. (That is, instead of beating simultaneously, the two ventricles beat slightly out of phase.) This asynchrony greatly reduces the efficiency of the ventricles in patients with heart failure, whose hearts are already damaged.  CRT re-coordinates the beating of the two ventricles by pacing both ventricles simultaneously. (Typical pacemakers only pace one ventricle, usually the right ventricle.) 

Previous clinical trials had shown that CRT can reduce hospitalization days in patients with heart failure, and can improve cardiac function, symptoms, and quality of life. Nonetheless, the government and insurance carriers have been slow to adequately reimburse for this therapy without better data documenting a reduction in total hospitalizations (i.e., forget making patients feel better - if it doesn't yield a cost savings they're not that interested) as well as data showing an improvement in survival.  The COMPANION study was devised to evaluate exactly these two endpoints.

In COMPANION, over 1600 patients with significant heart failure, including recent prior hospitalizations for heart failure, and intraventricular conduction delays or bundle branch block, were randomized to to receive optimal drug therapy, or optimal drug therapy plus CRT.  (Half the patients receiving CRT got a CRT device that also acts as an implantable defibrillator; the other half got CRT pacing alone.)

The formal presentation of the data from COMPANION will not be made until this spring at one of the major cardiology meetings.  However, the principal investigators and the sponsor (Guidant) held a telephone conference on November 21 to describe why the study was halted so suddenly.  They reported that patients receiving either kind of CRT device had more than a 20% reduction in the composite endpoint of the study (i.e., total hospitalizations and death from any cause.) They further reported a highly statistically significant 40% reduction in death among patients receiving the CRT-plus-defibrillator, and about half that death reduction in patients receiving CRT pacing alone.

Given this result, the Data Safety and Monitoring Board determined that, for ethical reasons, patients enrolled in COMPANION who did not receive the CRT device must now be offered CRT therapy.  Therefore, the study had to be terminated immediately.