ESC: CRT-D reduces heart failure events -- worth the expense?
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Despite the positive results, an accompanying editorial questioned the cost-effectiveness of employing such a treatment strategy.
During a 4.5-year period, Arthur J. Moss, MD, from the University of Rochester Medical Center in Rochester, N.Y., enrolled and followed 1,820 patients with ischemic or non-ischemic cardiomyopathy, an ejection fraction of 30 percent or less, a QRS duration of 130 msec or more and N.Y. Heart Association class I or II symptoms.
He and his colleagues randomly assigned patients in a 3:2 ratio to receive a CRT-D (1,089 patients) or an ICD alone (731 patients).
The primary endpoint was death from any cause or a nonfatal heart failure event (whichever came first). Heart failure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments, according to the authors.
During an average follow-up of 2.4 years, the MADIT-CRT investigators said the primary endpoint occurred in 17.2 percent of patients in the CRT-D group and 25.3 percent of patients in the ICD-only group. The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with non-ischemic cardiomyopathy.
According to the researchers, the superiority of CRT-D was driven by a 41 percent reduction in the risk of heart failure events, a finding that was evident primarily in a pre-specified subgroup of patients with a QRS duration of 150 msec or more. CRT-D was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction.
The researchers also reported that there was no significant difference between the two groups in the overall risk of death, with a 3 percent annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups.
According to the authors, the superiority of CRT-D therapy was found to be present in all patient sub-groups, including those with ischemic and non-ischemic types of heart disease, as well as in males and females, younger and older patients and those with mild and more advanced heart dysfunction.
The study authors wrote that the “difference in the frequency of heart failure events in the two study groups is not likely to be due to an increase in the rate of pacemaker-induced heart failure in the ICD-only group, since the demand pacing rate was programmed to 40 bpm, a backup bradycardia rate that has not been associated with an increased heart failure rate. The reduction in heart failure events with CRT-D was not associated with a reduction in mortality in this prevention trial.”
Commenting on the results, Moss said that CRT-D was “dramatically effective in this large study population, with a 34 percent reduction in the risk of all-cause mortality or heart failure. The benefit is dominated by a 41 percent reduction in heart failure events. These results validate a new indication for cardiac resynchronization therapy in the prevention of heart failure in at-risk asymptomatic or mildly symptomatic cardiac patients. It seems likely that this preventive CRT-D therapy will have widespread application and utilization."
In an accompanying NEJM editorial, Mariell L. Jessup, MD, from the cardiovascular division at the University of Pennsylvania School of Medicine in Philadelphia, wrote that it is “unlikely that less-symptomatic patients receiving CRT would have a significant reduction in mortality unless a large number of patients underwent prolonged follow-up.”
Also, Jessup noted that, according to the MADIT-CRT results, 12 patients would need to be treated to prevent a single heart-failure event.
As a result, she questioned its economic value. “An analysis that was based on data from the five longest CRT randomized trials revealed that the incremental cost per quality-adjusted life-year gained was $32,822. The incremental cost-effectiveness of combined CRT with ICD devices, as compared with CRT devices alone, has been markedly higher in most analyses,” Jessup wrote. “Is this money that could be spent more wisely?
“Given the sobering facts about the costs of healthcare confronting us now and in the future, it appears prudent that any expanded indication for CRT in less-symptomatic patients should be confined to patients with a QRS duration of more than 150 msec and in whom previous marked symptoms have been controlled with optimal medical therapy,” Jessup concluded.
Natick, Mass.-based Boston Scientific sponsored the trial. Prior to this year, Moss received honoraria from Boston Scientific for talks at scientific programs. However, he disclosed that he holds no stock in any device company, has never been a member of any corporate speakers' bureau, and since Dec. 1, 2008, has chosen not to accept honoraria from Boston Scientific for his professional activity. Jessup reported serving on an advisory board for Medtronic, but disclosed no other potential conflict of interest.