The HEART-FID trial, the largest study to date to investigate intravenous iron therapy in heart failure, compared ferric carboxymaltose (FCM) to a placebo in ambulatory patients with heart failure with reduced ejection fraction as well as iron deficiency. While the trial demonstrated a modest reduction in major clinical outcomes, including all-cause mortality, this difference was not statistically significant. This secondary analysis of the HEART-FID trial, led by CVC Co-Director Dr. Justin Ezekowitz, aimed to describe participant characteristics, identify mortality risk factors, and evaluate the effect of FCM versus placebo on all-cause and cardiovascular mortality, including post-hospitalization outcomes.
The researchers used multivariable models to identify factors associated with all-cause mortality in HEART-FID patients, considering key patient characteristics and treatment interactions from the primary study. All-cause mortality was assessed at 12 months and over the median 23.1-month follow-up period using Cox proportional hazard regression, a statistical method examining how factors influence the rate of events like mortality over time.
Among the 3,065 patients in the HEART-FID study, 737 all-cause mortality events occurred during the study, including 289 in the first year. Long-term follow-up mirrored the 12-month HEART-FID results, showing modest reductions in all-cause and cardiovascular mortality with FCM compared to placebo. N-Terminal pro B-type natriuretic peptide level (a marker of cardiac stress), country of enrollment, and 6-minute walk distance were identified as the strongest independent predictors of mortality at 12 months. Notably, treatment benefits varied by patient subgroup, with consistent positive effects observed in males of all ages and older females, but not in younger female patients. Finally, while not statistically significant, FCM appeared to show a modest benefit in reducing fatal events following heart failure hospitalization, a high-risk period for these patients. The researchers emphasize the importance of considering these study results when interpreting and applying the HEART-FID findings in clinical practice.
