At a late breaking clinical trials session, Dr. Bristow presented preliminary results of the COMParison of MedicAl, ResynchronizatioN, and DefibrillatION Therapies in Heart Failure (COMPANION). The study evaluated chronic resynchronization therapy, with or without an implantable defibrillator, in patients with heart failure and QRS widening. The primary hypothesis of this major clinical trial is that either therapy would lower morbidity and mortality.

The study included patients with New York Heart Association Class III or IV chronic heart failure and QRS width greater than 130 milliseconds. To be eligible for the trial, patients must have had a heart failure hospitalization within the past 12 months.

Investigators randomized the patients in a 1:2:2 fashion into one of three groups. The first group received only optimal pharmacological therapy for heart failure. The definition of optimal pharmacological therapy was diuretics, beta blockade, ACE inhibition or ARB substitution, spironolactone, and optionally, digoxin. The second group received this optimal medical therapy plus a biventricular cardiac resynchronization therapy device. The third received optimal therapy plus a resynchronization device and an implantable cardioverter defibrillator.

Dr. Bristow reported on 1,520 patients; 68% were men, the mean age was 72 years, and 75% had Class III heart failure. While more than 1,600 patients had enrolled, the trial met its efficacy trial for termination in November 2002. Investigators stopped tabulating efficacy endpoints soon after that.

The primary endpoint was time to all-cause mortality or non-elective hospitalization. There was a significant reduction in this endpoint for both the resynchronization group (18.6%, p=0.015) and in the resynchronization plus defibrillator group (19.2%, p=0.005).

Investigators found a highly significant reduction in mortality in the group of patients that received both the resynchronization device with defibrillator. There was a 43% reduction in mortality rate at 12 months. There was a trend toward reduction in mortality in the group of patients that received the resynchronization device but no defibrillator. There was a 24% reduction in mortality at 12 months.

Dr. Bristow and colleagues performed some further analysis and found a 34% reduction in time to mortality or heart failure hospitalization in the resynchronization group (p<0.001) and a 38.3% reduction in the resynchronization/defibrillator group (p<0.001).

While these are all preliminary data, the investigators believe they accurately reflect what will be the ultimate outcome of the trial.

One important question is whether either implantation strategy will be cost effective. Investigators have not undertaken economic studies yet. However, Dr. Bristow believes that both approaches would be cost effective. This is because heart failure hospitalizations are a major factor in the cost of heart failure care. In the COMPANION trial, both approaches provide a substantial reduction in heart failure hospitalizations.

A number of other recent trials have failed to show a benefit of some intervention on top of optimal medical therapy. Now, the COMPANION trial, plus the EPHESUS trial Dr. Pitt presented here at ACC, show the opposite. The results suggest that doctors can improve the outcomes in heart failure beyond what they might expect to see with today's standard medications.