A pilot evaluation of the long-term effect of combined therapy with intravenous iron sucrose and erythropoietin in elderly patients with advanced chronic heart failure and cardio-renal anemia syndrome: influence on neurohormonal activation and clinical outcomes.
BACKGROUND
The prognosis in elderly patients with advanced chronic heart failure (CHF) and cardio-renal anemia syndrome (CRAS) is ominous, and treatment alternatives in this subset of patients are scarce.


RESULTS
To assess the long-term influence of combined therapy with intravenous (IV) iron and erythropoietin (rHuEPO) on hemoglobin (Hb), natriuretic peptides (NT-proBNP), and clinical outcomes in elderly patients with advanced CHF and mild-to-moderate renal dysfunction and anemia (CRAS) who are not candidates for other treatment alternatives, 487 consecutive patients were evaluated. Of them, 65 fulfilling criteria for entering the study were divided into 2 groups and treated in an open-label, nonrandomized fashion: intervention group (27, combined anemia therapy) and control group (38, no treatment for anemia). At baseline, mean age was 74 +/- 8 years, left ventricular ejection fraction was 34.5 +/- 14.1, Hb was 10.9 +/- 0.9 g/dL, creatinine was 1.5 +/- 0.5 mg/dL, NT-proBNP was 4256 +/- 4952 pg/mL, and 100% were in persistent New York Heart Association (NYHA) Class III or IV. At follow-up (15.3 +/- 8.6 months), patients in the intervention group had higher levels of hemoglobin (13.5 +/- 1.5 vs. 11.3 +/- 1.1; P < .0001), lower levels of natural log of NT-proBNP (7.3 +/- 0.8 vs. 8.0 +/- 1.3, P = .016), better NYHA functional class (2.0 +/- 0.6 vs. 3.3 +/- 0.5; P < .001), and lower readmission rate (25.9% vs. 76.3%; P < .001). In the multivariate Cox proportional hazards model, combined therapy was associated with a reduction of the combined end point all-cause mortality or cardiovascular hospitalization (HR 95%CI 0.2 [0.1-0.6]; P < .001).


CONCLUSIONS
Long-term combined therapy with IV iron and rHuEPO may increase Hb, reduce NT-proBNP, and improve functional capacity and cardiovascular hospitalization in elderly patients with advanced CHF and CRAS with mild to moderate renal dysfunction.
Comín-Colet
Josep
J
Department of Cardiology, Heart Failure Program, Hospital del Mar (IMAS), Barcelona, Spain. jcomin@hospitaldelmar.cat
Ruiz
Sonia
S
Cladellas
Mercè
M
Rizzo
Marcelo
M
Torres
Adriana
A
Bruguera
Jordi
J
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D002908:Chronic Disease; D015331:Cohort Studies; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D000077605:Ferric Oxide, Saccharated; D005500:Follow-Up Studies; D005937:Glucaric Acid; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood*; D010865:Pilot Projects; D011446:Prospective Studies; D011994:Recombinant Proteins; D015996:Survival Rate; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome
D005290:Ferric Compounds; D018377:Neurotransmitter Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid