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. METHODS AND 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). CONCLUSION: 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.