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

Abstract

Background: The HEART-FID trial is the largest trial to test intravenous iron (ferric carboxymaltose [FCM]) versus placebo in patients with heart failure and iron deficiency. The results showed a modest but non-statistically significant reduction in important clinical outcomes, including all-cause mortality.

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

Methods: Data on patients enrolled in HEART-FID 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 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 with diabetes, atrial fibrillation, lower ejection fraction and estimated glomerular filtration rate, and a higher N-terminal pro b-type natriuretic peptide (NT-proBNP) level. 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 for older women than for other patient subgroups.

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.