MADIT-CRT: Cardiac resynchronization with defibrillator lowered risk for all-cause mortality, HF events

Risk reduction in the overall population was driven by a 41% reduction in risk for HF events.

European Society of Cardiology Congress 2009

Patients with mild or no cardiac symptoms who received a cardiac resynchronization device with a defibrillator had lower risk for all-cause mortality or HF than those with an implantable cardioverter defibrillator alone.

Researchers for the MADIT-CRT trial enrolled 1,820 patients with ischemic or nonischemic cardiomyopathy, left ventricular dysfunction, a wide QRS duration and NYHA Class I or II HF. Patients were randomly assigned at a 3:2 ratio to either receive a CRT device with an ICD (n=1,089) or an ICD alone (n=731). The endpoint was all-cause death or nonfatal HF events. Patients were followed for an average of 2.4 years.

There was a 34% decrease in the risk for death or nonfatal HF in patients in the CRT plus ICD group vs. the ICD alone group. The primary study endpoint occurred in 372 patients, including 187 (17.2%) in the resynchronization plus ICD group and 185 (25.3%) patients in the ICD alone group (HR=0.66; 95% CI, 0.52-0.84). For the total population in both the ischemic and nonischemic cardiomyopathy subgroups, the results indicated that benefit from the CRT was driven by a 41% decrease in the risk for HF. The researchers reported no significant difference in benefit between patients with ischemic and nonischemic cardiomyopathy.

“These results validate a new indication for cardiac resynchronization therapy in the prevention of HF in at-risk asymptomatic or mildly symptomatic cardiac patients,” Arthur J. Moss, MD, a professor of medicine at the University of Rochester Medical Center in New York, said in a press release. “It seems likely that this preventive cardiac resynchronization with defibrillator therapy will have widespread application and utilization.”

In the discussant report, Guenter Breithardt, MD, a professor of medicine at Universitat Muenster Medizinische Klinik und Poliklinik in Muenster, Germany, said that the results of MADIT-CRT were comparable to those of a previous trial (REVERSE, which failed to meet its primary endpoint of reduced risk of first HF hospitalization at 12 months) and that they opened the larger issue of whether cardiac resynchronization therapy can retard the long-term progression of disease to lower mortality in patients with NYHA Class I and II HF.

“MADIT-CRT has shown that cardiac resynchronization therapy may delay disease progression in NYHA Class I or II patients through LV remodeling,” Breithardt wrote. “This is consistent with a prior smaller trial (REVERSE; 610 patients) which, however, did not reach statistical significance of an HF clinical composite response that compared only the percentage of patients worsened (primary endpoint). However, secondary endpoints were in line with the much larger MADIT-CRT trial results concerning LV remodeling and reduction in the need for HF hospitalizations.”

The study results were also published in the New England Journal of Medicine. - Eric Raible

This study was performed superbly by experienced investigators. In 1,820 patients with ischemic or nonischemic cardiomyopathy who had mild (class I or II) HF symptoms, but significantly reduced LV systolic function (ejection fraction =30%) and prolonged QRS (130ms or more), they compared CRT with an ICD vs. an ICD alone. During an average follow up of 2.4 years, they found no difference in mortality (3% annual mortality in both groups), but a 41% reduction in HF events, primarily in those with a very long (150ms or more) QRS duration. In an editorial accompanying the published study, Mariell Jessup, MD, notes that 12 patients would have to be treated to prevent a single HF event without a mortality benefit and questions whether that is money wisely spent, given the cost of such therapy. She suggests that CRT in less symptomatic patients be for those who were significantly symptomatic in the past, now controlled with drug therapy, and with a QRS 150ms or more. This seems to be a reasonable suggestion. This study may widen the net to capture more patients for CRT-ICD. Whether or not that is appropriate should be discussed. It is likely that our indications for ICD, and now maybe for CRT as well, may be too broad and nonspecific, because only a third or so of patients with ICD indications receive the device because many physicians are concerned about appropriate utilization and only about a third of those who receive an ICD actually use the device after several years. We need better patient-specific identifications for who actually will benefit from these expensive devices.

— Douglas P. Zipes, MD

Cardiology Today Section Editor

MADIT-CRT joins many trials confirming the benefit of CRT in patients with LV dysfunction and a prolonged QRS duration. MADIT-CRT is distinguished from other trials in this area by its inclusion of patients who had no or minimal symptoms at enrollment. An important characteristic of the study population is that 10% of patients in each study group had a history of NYHA Class III or IV HF at least three months before randomization. Thus, MADIT-CRT enrolled patients who were not always asymptomatic or minimally symptomatic. Combining this with the observation above QRS duration, prescription of a CRT device for a patient who is asymptomatic or minimally symptomatic might best be reserved for those with a QRS duration of at least 150 ms and a history of more symptomatic HF that has been treated by optimizing medical therapy. This may enrich the population expected to derive the most gain in a cost effective fashion from CRT. However, this group may well comprise less than five percent of patients with an indication for a primary prevention ICD.

- Andrew Epstein, MD

Cardiology Today Editorial Board member

For more information:

• Moss AJ. #3592-3593. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2009; Barcelona, Spain.
• Moss AJ. N Engl J Med. 2009;361:1-10.