Abstract and Introduction
Abstract
Background. Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) frequently requires parenteral iron replacement, but existing therapies often require multiple administrations. We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose (FCM), a non-dextran parenteral iron permitting large single-dose infusions, versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD.
Methods. A total of 2584 participants were randomized to two doses of FCM 750 mg in one week, or iron sucrose 200 mg administered in up to five infusions in 14 days. The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56. The primary composite safety endpoint included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina, congestive heart failure, arrhythmias and hyper- and hypotensive events.
Results. The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group (95% CI, 0.13–0.28). Similar results were observed across all subgroups, except Stage 2 CKD. More subjects in the FCM group achieved a hemoglobin increase of ≥1.0 g/dL between baseline and Day 56 (48.6 versus 41.0%; 95% CI, 3.6–11.6%). There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint, including the major adverse cardiac events of death, myocardial infarction, or stroke. A significant difference in the number of protocol-defined, predominantly transient hypertensive episodes was observed in the FCM group.
Conclusions. Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia.
Introduction
Iron-deficiency anemia affects more than 800 000 patients with chronic kidney disease (CKD) in the USA and is associated with substantial mortality, morbidity and reduced quality of life. Among patients with CKD, the prevalence and severity of anemia are directly related to the degree of renal failure. Although decreased erythropoietin production contributes to anemia in patients with CKD, iron deficiency due to dietary restriction, occult blood loss from the gastrointestinal tract, frequent laboratory testing and accelerated hemolysis also play significant roles.
Intravenous (IV) iron therapy is an accepted treatment regimen for the management of iron-deficiency anemia in patients with CKD. Parenteral iron therapies available in the USA include iron dextran, sodium ferric gluconate (SFG), iron sucrose and ferumoxytol. Typical therapeutic courses of iron dextran, SFG or iron sucrose require 5–10 injections of 100–200 mg doses of each. Ferumoxytol (Feraheme; AMAG Pharmaceuticals, Inc., Cambridge, MA), is an iron oxide with a carbohydrate coating that was approved by the Food and Drug Administration (FDA) for the treatment of anemia in CKD in 2009. It is given as two 510-mg injections 3–8 days apart for a maximum treatment dose of 1020 mg. Thus, with the exception of ferumoxytol, most available IV iron preparations require frequent administrations that increase costs and are more inconvenient to patients and healthcare providers, and may thus reduce compliance.
Ferric carboxymaltose (FCM) (Injectafer; Luitpold Pharmaceuticals, Shirley, NY) is an IV iron preparation whose properties permit administration of even larger single doses (750 mg) over short periods of time for a maximum treatment dose of 1500 mg. Previous studies have shown that FCM is efficacious and well tolerated in a variety of settings, including CKD, congestive heart failure, inflammatory bowel disease, anemia related to the postpartum period, heavy menstrual bleeding and anemia associated with cancer and chemotherapy.
In our study, the Randomized Evaluation of Efficacy and Safety of FCM in Patients with Iron-Deficiency Anemia and Impaired Renal Function (REPAIR-IDA), we sought to evaluate the cardiovascular safety and efficacy of IV FCM compared with IV iron sucrose in patients with iron-deficiency anemia and non-dialysis-dependent CKD (NDD-CKD).