Methods
death, HF, AHF, Cardiomyopathy, AFFIRM-AHF, Chronic kidney disease, diabetes
ADVERSE EVENTS, EVENT, IRON DEFICIENCY, CARDIOMYOPATHY, SECONDARY, INTERACTION, REGRESSION, EVENTS, CHRONIC KIDNEY DISEASE, DIABETES
The design and primary results of the international, multicenter, double-blind, placebo-controlled, phase 4 randomized AFFIRM-AHF trial are already published [AFFIRM-AHF included patients aged ≥ 18 years who had been hospitalized with signs and symptoms typical of AHF, treated with a minimum of 40 mg IV furosemide (or equivalent IV diuretic), and who had concomitant iron deficiency (defined as serum ferritin < 100 μg/L, or serum ferritin 100–299 μg/L with transferrin saturation [TSAT] < 20%) and a left ventricular ejection fraction < 50%. Patients were randomly assigned (1:1) to receive IV FCM or placebo, with the first dose administered shortly before discharge and the second dose administered at Week 6 (dose based on screening hemoglobin [Hb] and body weight values, as detailed previously [The primary endpoint was a composite of total HF hospitalizations and CV death up to 52 weeks of follow-up. Secondary clinical endpoints (total CV hospitalizations and CV death; CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalizations or CV death) were also evaluated up to 52 weeks. Other endpoints included changes in disease-specific QoL (assessed using the self-administered 12-item Kansas City Cardiomyopathy Questionnaire [KCCQ-12] overall summary score [OSS] and clinical summary score [CSS]) from baseline to Weeks 2, 4, 6, 12, 24, 36, and 52, and laboratory values (serum ferritin, Hb, and TSAT) from baseline to Weeks 6, 12, 24, and 52. Safety endpoints included a summary of adverse events (AEs).All analyses were based on data for AFFIRM-AHF patients with known diabetes status at baseline, with the safety analysis set (SAS) used for safety and laboratory endpoint analyses and the modified intention-to-treat (mITT) population used for all other endpoint analyses. Given the limited number of patients in the subgroups stratified by diabetes status, baseline characteristics were descriptively summarized as mean (standard deviation [SD]) for continuous variables and n (%) for discrete variables, and statistical significance was not assessed. Chronic kidney disease was determined by investigator-indicated status (yes/no) in the AFFIRM-AHF eCRF. Primary and secondary outcomes with FCM vs placebo within each subgroup were analyzed using a negative binomial model for recurrent endpoints (presented as event rate ratios [RRs] and 95% confidence intervals [CIs]) and a Cox regression model for time to first event endpoints (presented as hazard ratios and 95% CIs). P-values for treatment effect within the subgroups by diabetes status are nominal and descriptive only. Interaction p-values (pIn each diabetes subgroup, mean (standard error) changes from baseline in KCCQ-12 OSS and CSS and in laboratory values (serum ferritin, Hb, and TSAT) with FCM vs placebo were compared at each time point using repeated measures ANOVA. P-values for treatment effect within the subgroups by diabetes status are nominal and descriptive only. Interaction p-values evaluating the interaction between diabetes status and the effect of FCM vs placebo on KCCQ-12 OSS and CSS at Week 24 (end of treatment period) were generated. AEs were descriptively summarized in each subgroup and treatment arm as number of subjects with events (%) and number of events. Analyses were not adjusted for multiplicity. For all analyses, SAS version 9.4 (SAS Institute, Inc., Cary, NC, USA; 2000–2004) was used, with p-values < 0.05 considered statistically significant.