COMPANION was a parallel, randomized clinical trial in 1600 patients with moderate or severe heart failure with QRS >120 ms and P-R interval >150 ms. Entry criteria stipulated that patients had to have been hospitalized at least once in the past year for heart failure management, to have had an outpatient visit in which inotropes or a vasoactive infusion were administered continuously for at least four hours, or to have had an emergency room visit of at least 12 hours during which intravenous heart failure medications were administered.

Patients were randomized in a 1:2:2 fashion to optimal medical therapy (including beta blockers, diuretics, ACE inhibitors or ARBs, spiralactone, and/or digoxen), optimal drug therapy plus CRT, or optimal drugs plus a CRT with ICD (CRT-D).

Bristow reported that the primary end point of the study, a combination of all-cause death and all-cause hospitalizations over 12 months, was significantly reduced by 19% for both the CRT and CRT-D arms of the study. CRT alone was also associated with a nonsignificant trend toward a 23.9% reduction in all-cause mortality, a secondary end point of the study, while the addition of an ICD to CRT increased the mortality reduction to 43.4%, a highly significant result. Hospitalizations related to device implantations were not considered for the purposes of the comparative analysis.

When results were examined according to heart failure etiology, the investigators found no significant differences in treatment effects between patients with ischemic and nonischemic cardiomyopathy.

"Reduction in the combined end points of death plus all-cause, cardiovascular, or heart failure hospitalizations was likely due to CRT, since CRT and CRT-D resulted in similar effect sizes," Bristow noted.

He added, "Based on a reduction in the primary end point that included all hospitalizations, CRT or CRT-D would likely be cost-effective in as much as heart failure hospitalizations are a major determinant of heart failure care costs, although this would need to be confirmed in further studies."

Asked by Dr Inderjit S Anand (Minneapolis, MN), who comoderated the late-breaking session, what he would recommend for a patient who matched the COMPANION entry criteria, Bristow reiterated that the data were not fully analyzed and that the final results "might shed light on things like subgroups and recommendations."

I think at the end of the day it's going to come down to a personal issue involving individual patients.

He continued, "I think at the end of the day it's going to come down to a personal issue involving individual patients. We have clinical trial data with large numbers of patients that show probabilities of things, but individual patients have individual characteristics that are important in terms of choice of device. For example, CRT clearly reduces hospitalizations, and previous data have shown that [fewer hospitalizations] improves quality of life. CRT-D has a greater effect on mortality, but not all patients want to live longer, they just want to feel better, so that would be one obvious consideration."

To heartwire, Bristow pointed out that for "those who just want to get up and do more and stay out of the hospital, living longer is not the issue. On the other hand, if they get a CRT, and they go out and improve and start to think about living longer, you can always upgrade the device."

Commenting on the COMPANION trial for heartwire, Dr Milton Packer (Columbia University, New York City) pointed out that the COMPANION results apply only to a small proportion of heart failure patients. "The patient population studied in COMPANION represents a pretty small slice of the overall population with heart failure, because we're talking about class III/IV patients with a wide QRS and LV dysfunction. My guess is we're probably talking about 250000 patients in the US, out of 5 million heart failure patients."

Packer was particularly "encouraged" by the CRT-D results, noting that patients treated with a CRT-D in COMPANION enjoyed similar benefit, regardless of whether their underlying cardiomyopathy was ischemic in origin. "In the past we've had only defibrillator data in ischemic patients, so this was the first clue that we might in fact be seeing an effect of defibrillators in nonischemic cardiomyopathies as well."

He added that it will be important to know exactly how many deaths occurred in the treatment arms, since that data wasn't presented. "Are we talking about 200 deaths, or 300 deaths, or are we talking about 50 or 100 deaths? That would be very important to find out."

By contrast, the CRT data were more "confusing," Packer told heartwire, primarily because CRT was credited with the reduction in all-cause hospitalizations. The problem with this, Packer said, is that hospitalizations related to device implantation were not included in the comparison.

"This is postrandomization censoring, and we know from other trials that postrandomization censoring causes biases, and it's particularly worrisome because, if a patient were hospitalized for a device and went home in 24 hours, did the investigators count that? I asked the investigators and they said no. Was it counted if a patient were hospitalized for a device and had a complication and stayed in the hospitalized for days and weeks? They said no. I think if you censor events in the first week for the device group, you have to censor the control group for the same period of time, and it doesn't appear that they did that."

This decision to discount device-related hospitalizations in the primary analysis will have to be taken into account in cost efficacy studies, Packer observed. Responding to Bristow's predictionto be confirmed in further studiesthat the cost of the devices would be offset by the number of hospital visits avoided, Packer said, "If they want to do an economic analysis here, they're going to have to count all the hospitalizations for the device implantation that they have thrown out of the primary analysis. I'm not certain I'd be so bold as to make a prediction as to how that would turn out. My personal sense is that it's not a slam dunk. You can rationalize spending a lot of money if what we're talking about is saving lives, but here, the major reason to use CRT is to reduce hospitalizations, and to put in the device you have to hospitalize the patient."