Prediction and Longer-Term Outcomes of All-cause and Cardiovascular Mortality in the HEART-FID Trial.

Abstract

Background: The HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose [FCM] as Treatment for Heart Failure with Iron Deficiency) is the largest trial to test intravenous iron (ferric carboxymaltose [FCM]) vs placebo in patients with heart failure and iron deficiency. The results showed a modest but nonstatistically significant reduction in important clinical outcomes, including all-cause mortality.

Objectives: We sought to understand the factors associated with all-cause mortality.

Methods: Data concerning patients enrolled in the HEART-FID trial were used to determine factors associated with all-cause mortality via multivariable models. The models included key clinical characteristics, including treatment interactions identified in the primary analysis (age by sex and country of enrollment). All-cause mortality at 12 months and over the full duration of follow-up (median 23.1 months) was evaluated by using Cox proportional hazard regression.

Results: A total of 3065 patients had 737 all-cause mortality events over the duration of the trial, with 289 events occurring in the first 12 months. Fewer patients randomized to FCM died by 12 months compared with the placebo group (131 receiving FCM vs 158 receiving placebo; hazard ratio 0.82 [95% confidence interval: 0.65-1.04]). Patients who died were more likely to be older and to have diabetes, atrial fibrillation, lower ejection fractions and estimated glomerular filtration rates and higher N-Terminal pro B-type natriuretic peptide (NT-proBNP) levels. The 3 multivariable factors most strongly associated with all-cause mortality at 12 months were NT-proBNP level, country of enrollment and 6-minute walk test distance. Similar results were seen for predicting all-cause mortality over the entire follow-up; the addition of an age × sex × FCM interaction yielded statistically significant results, with greater association of benefit from FCM found in older women than in other subgroups of patients.

Conclusion: FCM, compared with placebo, was associated with a potentially clinically meaningful (but not statistically significant) reduction in all-cause mortality, with key predictors of mortality being natriuretic peptide level, country of enrollment and 6-minute walk test distance.