Chronic Heart Failure (EFFECT-HF): A Randomized, controlled study

Presented on AHA Scientific Sessions 2016 by: D.J. van Veldhuisen, University Medical Center Groningen, Groningen, Netherlands

Restoring iron deficiency with IV ferric carboxymaltose (FCM) improves exercise capacity in patients with heart failure (HF).

Iron deficiency is a frequent comorbidity in patients with stable HF and in patients that are admitted to the hospital due to worsening HF. This is associated with impaired functional capacity, a poor quality of life and increased mortality. Iron deficiency can result from reduced oxygen delivery due to a hemoglobulin (Hb) decrease or from impaired O₂ utilization through the reduction of aerobic enzymes. Both a reduction in O­₂ delivery and utilization results in reduced peak oxygen consumption (pVO₂). pVO₂ is an important prognostic factor in HF patients and even a modest increase has been associated with a more favourable outcome. Prior studies including FAIR-HF and CONFIRM-HF already confirmed benefit of FCM in iron deficient HF patients.

To validate this, the multicentre, open label, randomized, assessor-blinded and standard of care-controlled EFFECT-HF trial assessed whether restoring iron deficiency using IV FCM would improve cardiopulmonary exercise tolerance in symptomatic HF patients. Therefore, the maximum pVO₂ was measured in 174 patients with HF NYHA class II/III and a left-ventricular ejection fraction (LVEF) ≤45%, a pVO₂ of 10-20 mL/kg/min, BNP > 100 pg/mL and/or NT-proBNP >400 pg/mL, a Hb <15 g/dL and iron deficiency (serum ferritin <100 ug/L or 100-300 ug/L if TSAT <20%). Patients were randomized to FCM, which was administered at day 0, week 6 and week 12 or standard of care (SoC). At week 24, the pVO­₂ was measured.

The results showed that the iron-related parameters ferritin, TSAT and Hb were all enhanced from baseline in FCM-treated patients, whereas sTfR was reduced in these patients. These differences were significantly different from differences observed in SoC patients. Moreover, the primary endpoint pVO­₂ was improved in FCM-treated patient compared to SoC patients; the adjusted changes from baseline were approximately -0,2 mL/kg/min for treated patients and -1,2 mL/kg/min for SoC patients (p=0.02). Furthermore, the carbon dioxide production relationships (VE/VCO₂ slope) were comparable between both groups. On the other hand, the numbers of hospitalizations slightly increased from 15.3 to 30.7%, whereas the mortality was 0% for FCM-treated patients and 4.7% for SoC patients. Also the frequency of adverse events (AEs) was higher in FCM-treated patients. This concerned any AE (60% vs. 48.2% for SoC), severe AE (14.8% vs. 9.4% for SoC), serious AE (31.8 vs. 18.8% for SoC), treatment-related event (9.1% vs. none for SoC) and severe treatment-related AE (3.4% vs. non for SoC). In contrast, AEs leading to study drug withdrawal (2.3% vs. 5.9% for SoC) or death (none vs. 5.9%) were lower in FCM-treated patients.

Overall, there was as significant improvement in peak VO₂ for patients treated with FCM compared to SoC patients. This shows that FCM improves exercise capacity and symptoms and confirm and extend the findings of previous FCM study results.

-Our reporting is based on the information provided during the AHA congress –