Responder analysis for improvement in 6-min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency

Abstract

Aim: Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR-HF and CONFIRM-HF assessed the likelihood of improvement or deterioration in 6-min walk test (6MWT) among iron-deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).

Methods and results: Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6-37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57-2.96]; p < 0.0001), ≥30 m (2.00 [1.44-2.78]; p < 0.0001), and ≥40 m (2.29 [1.60-3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38-0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24.

Conclusion: Ferric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron-deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF.

Keywords: 6-min walk test; CONFIRM-HF; FAIR-HF; Ferric carboxymaltose; Heart Failure; Responder.

Figure 1

Mean change from baseline in 6‐min walk test (6MWT) with ferric carboxymaltose (FCM) versus placebo at weeks 12 and 24 – fixed‐effects model. Least‐square (LS) mean difference based on a fixed‐effects mixed model for repeated measures analysis adjusted for study, baseline 6MWT score, age, estimated glomerular filtration rate, diabetes status, sex, and left ventricular ejection fraction. Since only six patients are from Latin America and the remainder are from Europe, region was not included in the model. In FCM and placebo groups, patient numbers were 418 and 289, respectively, at week 12 and 415 and 283, respectively, at week 24. CI, confidence interval; SD, standard deviation.

Figure 2

Responder analyses across minimal clinically important difference thresholds for 6‐min walk test (6MWT). Odds ratios (ORs) with 95% confidence intervals (CIs) and p‐values were obtained from logistic regression models, including treatment group, study, and the following baseline factors: 6MWT distance, age, estimated glomerular filtration rate, diabetes status, sex, and left ventricular ejection fraction. Patients were from Europe and Latin America, but since only six patients were from Latin America, region was not included in the model. Patients who had died or were hospitalized at weeks 12 and 24 were counted as deteriorated/non‐responder at the respective time point. FCM, ferric carboxymaltose; PBO, placebo.

Figure 3

Response stability analysis – change in 6‐min walk test (6MWT) response between week 12 and week 24. Patients who had died or were hospitalized at weeks 12 and 24 were counted as deteriorated/non‐responder at the respective time point. N = the number of patients that had non‐missing 6MWT information available at both week 12 and week 24. Changes in 6MWT at week 12 and week 24 are with respect to baseline. FCM, ferric carboxymaltose.