Impact of ischaemic aetiology on the efficacy of intravenous ferric carboxymaltose in patients with iron deficiency and acute heart failure: insights from the AFFIRM‐AHF trial

AIMS: In AFFIRM‐AHF, intravenous ferric carboxymaltose (FCM) reduced heart failure (HF) hospitalisations and improved quality of life versus placebo in iron‐deficient patients stabilised after an acute HF episode. This analysis explored the effects of FCM versus placebo in patients with ischaemic and non‐ischaemic HF aetiology. METHODS AND RESULTS: We included 1082 patients from AFFIRM‐AHF: 590 with ischaemic HF (defined as investigator‐reported ischaemic HF aetiology and/or prior acute myocardial infarction and/or prior coronary revascularisation) and 492 with non‐ischaemic HF. The prevalences of male sex, comorbidities, and history of HF were higher in the ischaemic versus non‐ischaemic HF subgroup. Annualised event rates for the primary composite outcome of total HF hospitalisations and cardiovascular death with FCM versus placebo were 65.3 versus 100.6 per 100 patient‐years in the ischaemic HF subgroup (rate ratio [RR] 0.65, 95% confidence interval [CI] 0.47–0.89, p = 0.007) and 58.3 versus 52.5 in the non‐ischaemic HF subgroup (RR 1.11, 95% CI 0.75–1.66, p = 0.60) (p (interaction) = 0.039). An interaction between HF aetiology and treatment effect was also observed for the secondary outcome of total HF hospitalisations (p (interaction) = 0.038). A nominal increase in quality of life, assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire, was observed with FCM versus placebo, within each subgroup. CONCLUSIONS: Heart failure hospitalisations and cardiovascular deaths occurred at a higher rate in patients with ishaemic versus those with non‐ischaemic HF and were reduced by FCM versus placebo only in ischaemic patients. Further studies are needed to assess the role of aetiology in FCM efficacy.