AMSTERDAM – , but the study failed to meet the specified more rigorous definition of significance (P = .01) on the primary hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance.
The trial, which investigated intravenous ferric carboxymaltose treatment vs. placebo, also showed no statistical difference in the main secondary endpoint: time to cardiovascular death or first heart failure hospitalization.
It was hoped that HEART-FID, the largest study to date to look at intravenous iron supplementation in heart failure, would confirm benefits suggested in previous smaller studies, but its modest results seem to have, if anything, caused more uncertainly on whether supplementing iron is actually worthwhile.
The HEART-FID trial was presented at the annual congress of the European Society of Cardiology and simultaneously published online in the New England Journal of Medicine.
Another presentation at the ESC Congress reported a pooled meta-analysis of all the intravenous iron supplementation studies, including HEART-FID. This showed a significant reduction in one coprimary endpoint (cardiovascular hospitalization/CV death) but not in the other (heart failure hospitalization/CV death), which is the more traditional and well-recognized endpoint in heart failure trials.
The meta-analysis was also published online in the European Heart Journal.
HEART-FID lead investigator, Robert J. Mentz, MD, Duke University, Durham, N.C., said the totality of the evidence showed clinical benefits of intravenous iron supplementation with intravenous ferric carboxymaltose.
“I worry that people will focus on a P value rather than the actual clinical benefits seen across all the studies,” Dr. Mentz said in an interview. “Technically, this study was neutral in respect to the primary endpoint, but when we look at all the evidence with respect to ferric carboxymaltose, including this new pooled analysis, this does support clinical benefits.”
Comoderator of the ESC Hotline session at which the trial was presented, John McMurray, MD, University of Glasgow (Scotland), thought the trial had “muddied the waters a bit” on the issue of iron supplementation in heart failure.
“I would say we are in a less clear position on iron supplementation now than we were a few months ago. Those clinicians who have believed that checking iron levels and supplementing iron in those who are low is the right thing to do may now be wondering about that,” he told this news organization.
Dr. McMurray noted that initial impressions of the data from both HEART-FID and the meta-analysis suggested some benefit of intravenous iron on CV death/heart failure hospitalization in the first year, but on longer term follow-up, that benefit was less evident.
“We need to look further into why there is that discrepancy,” he said. “This could be a statistical phenomenon or could be something to do with the frequency of redosing over the longer term.”
He explained that several previous studies of intravenous iron supplementation in heart failure have reported apparent convincing benefits on quality of life and functional capacity, but there has been some uncertainty on this because of the difficulty in producing a placebo for intravenous iron.
“So, it would have been great to have some additional confirmation of these benefits and on harder endpoints,” he said, “but even in HEART-FID, there was only a small nonsignificant benefit in walking distance.”