November 14th, 2010
A Life-RAFT for Patients with HF?
CardioExchange welcomes Arthur Moss, Professor of Medicine at the University of Rochester School of Medicine and lead investigator of the MADIT-CRT trial, to discuss his New England Journal of Medicine editorial on the RAFT trial, in which patients with mild-to-moderate HF were randomized to receive either an ICD alone or ICD plus CRT.
It seems notable that the vast majority of patients in the RAFT and MADIT-CRT trials had left bundle branch block (LBBB). To what extent do you think the results of both trials are actually driven by patients with LBBB?
The results in MADIT-CRT were driven by LBBB, and that is why the FDA approved the CRT-D indication for the MADIT-CRT enrollment criteria, which includes LBBB. In the RAFT trial, patients with LBBB had a better result than patients with each of the other QRS morphologies. Thus, I think that LBBB is the prime indication for CRT-D therapy in patients who qualified for MADIT-CRT or RAFT.
RAFT included individuals with a QRS duration >=120 msec, compared to the MADIT-CRT cut-point of >=130 msec. However, the mean QRS of all enrolled patients was still close to 160 msec. Do you think this fact should influence the way we consider patients who have QRS durations on the narrower end of the spectrum?
Yes. Patients with LBBB get the best results. However, in MADIT-CRT, women with QRS >130 msec obtained a favorable result even without LBBB. Thus, there are some subsets of patients who obtain benefit with QRS durations in the narrower end of the spectrum, but that may be too much “subsetting”. Thus, I favor the presence of LBBB as the primary indication for CRT-D therapy.
In MADIT-CRT, women seemed to respond better to CRT than men. In RAFT, the sex interaction is not quite significant, although the overall proportion of women in the trial was smaller than in MADIT-CRT. Do you think there is likely a real difference in the treatment effect between women and men? If so, are there any thoughts on what might account for this difference?
Women obtained a dramatically better result than men with CRT-D vs. ICD therapy in MADIT-CRT, but this finding was borderline in RAFT. I interpreted the less significant findings in RAFT as being due to a power issue because the percentage of women in their CRT-D arm was only 15% (compared to 25% in MADIT-CRT). There may be other factors operating (LBBB, ischemic vs. non-ischemic cardiomyopathy, age, etc.), so I look forward to the gender-related substudies from RAFT. Our gender-related substudy in MADIT-CRT has been accepted for publication in the Journal of the American College of Cardiology with anticipated publication in December 2010. In MADIT-CRT, the female benefit from CRT-D persisted even after adjusting for all relevant co-variates, including LBBB.
Do you think that results from MADIT-CRT and, now, RAFT are ready for incorporation into clinical guidelines? If so, how do you think these results should be best incorporated?
With these two major studies showing very similar results and the findings from the REVERSE trial consistent with these two larger studies, I do believe that clinical guideline recommendations should be developed by the AHA, ACC, and HRS. I would keep it simple by following the recommendations of the FDA, with criteria including EF<30%, NYHA class I/II symptoms, QRS >130 msec, and LBBB on ECG. Unfortunately, no U.S. patients were enrolled in the RAFT study.
Note: For more information on RAFT, see our news story .