Association between sex and efficacy of intravenous ferric carboxymaltose in patients with acute heart failure and iron deficiency: an AFFIRM-AHF subgroup analysis

Abstract

Abstract Background/Introduction Heart failure (HF) pathophysiology, clinical presentation and treatment response is known to differ between males and females (1). In the AFFIRM-AHF trial, intravenous (IV) ferric carboxymaltose (FCM) reduced the risk of HF hospitalisations and improved quality of life vs placebo in patients with iron deficiency who had stabilised following an acute HF (AHF) episode (2,3); the effect of sex on outcomes with iron-repletion therapy in these high-risk patients has not been fully explored. Purpose To investigate the interaction between sex and the effects of FCM vs placebo on clinical outcomes in the AFFIRM-AHF population. Methods In AFFIRM-AHF, patients with left ventricular ejection fraction <50% and iron deficiency (defined as serum ferritin <100 ng/mL, or 100–299 ng/mL if transferrin saturation is <20%) who had stabilised following recent hospitalisation for AHF were randomised 1:1 to receive IV FCM or placebo for up to 24 weeks.2 The primary endpoint was a composite of total HF hospitalisations and cardiovascular (CV) death up to Week 52; secondary endpoints are listed in the Figure.2 In this prespecified analysis, AFFIRM-AHF patients were stratified into male and female subgroups and the interaction between sex and clinical outcomes with FCM vs placebo was explored. Results Of the 1108 patients included in the AFFIRM-AHF full analysis set, 614 (FCM: 314; placebo: 300) were male and 494 (FCM: 244; placebo: 250) were female. At baseline, a New York Heart Association functional class of III and above was more common in females (59.0%) than in males (48.4%). For the primary endpoint, the adjusted annualised event rate per 100 patient-years with FCM vs placebo was 53.3 vs 83.3 in males (rate ratio [RR] 0.64; 95% confidence interval [CI] 0.46–0.89) and 63.1 vs 60.3 in females (RR 1.05; 95% CI 0.72–1.53) (Figure). For all secondary endpoints except time to CV death, effect sizes in male and female subgroups were similar to those for the primary endpoint. The interaction between sex and treatment effect was non-significant for the primary endpoint (P-interaction=0.054) but reached significance for the secondary endpoints of total CV hospitalisations and CV death (P-interaction=0.024) and time to first HF hospitalisation or CV death (P-interaction=0.043). Conclusion(s) The results of this exploratory subgroup analysis suggest that iron deficiency treatment with IV FCM following an AHF episode may be more effective in males than in females; this may be related to baseline differences between sex subgroups, beyond the factors adjusted for in this analysis.Figure