Anemia Correction in Heart Failure
Anemia Correction in Heart Failure
Abstract & Commentary
Synopsis: The treatment of anemia in patients with moderate-to-severe heart failure due to systolic dysfunction resulted in improvements in symptoms, LVEF, diuretic use and hospital use compared to an untreated group.
Source: Silverberg DS, et al. J Am Coll Cardiol. 2001; 37:1775-1780.
Although anemia is frequently observed in patients with severe heart failure, its correction is of unknown value in treatment. Thus, Silverberg and associates performed a prospective, randomized trial of anemia correction in 32 patients with New York Heart Association (NYHA) class III-IV heart failure and left ventricular ejection fraction (LVEF) < 40% despite maximally tolerated heart failure medications, who had hemoglobin (Hgb) levels between 10 and 11.5 g%. The treatment group (n = 16) was given erythropoietin (Epo) and intravenous iron to raise their Hgb to > 12.5 g%. Heart failure medications with the exception of diuretics were held constant during the 5-12 month (mean, 8 months) study period. There were no deaths in the treated group, but 4 of 16 died of heart failure in the control group. NYHA class decreased in all but 1 patient in the treatment group who remained the same. By contrast, only 1 patient in the control group improved, 8 stayed the same, and 7 worsened. LVEF increased in the treated group (+5.5%) and decreased in the control group (-5.4%). Furosemide dose decreased in the treated group (-72 mg/d) and increased in the controls (+43 mg/d) Finally, hospital days decreased by 79% in the treated group and increased by 58% in the controls. All these differences were statistically significant. Silverberg et al concluded that the treatment of anemia in patients with moderate-to-severe heart failure due to systolic dysfunction resulted in improvements in symptoms, LVEF, diuretic use, and hospital use compared to an untreated group.
Comment by Michael H. Crawford, MD
The major finding in this study is that even the correction of relatively mild anemia in heart failure patients improved cardiac function and clinical status. The mean Hgb was increased from 10.3 to 12.9 g%, a modest but statistically significant change. Also, the clinical improvements were observed despite a reduction in diuretic doses in the treatment group and increases in the control group. It could not be said that the patients were inadequately treated since > 85% were on digoxin, > 75% nitrates, > 90% aldosterone antagonists, > 68% beta blockers, > 87% angiotensin converting enzyme inhibitors, and 7-13% were on angiotensin receptor blockers. Compared to other heart failure studies, this is as good as it gets for maximal medical therapy.
The anemia therapy was somewhat unique, especially for cardiologists. Epo 4000u was given subcutaneously starting at once per week and increasing or decreasing the frequency depending on the response. The frequency ranged from 3 times a week to once every 3 weeks during the maintenance phase of the study. Intravenous iron 200 mg over 60 minutes was given every 2 weeks to start and the frequency was decreased depending on the response. Silverberg et al have considerable experience with this therapy and have had no serious adverse effects in > 1200 patients over 6 years. Hypertension, the most common potentially serious complication of Epo, was not observed in this study.
Silverberg et al argue that Epo may be superior to transfusion in heart failure patients, not only because it avoids transfusion reactions, but because of certain cardiovascular effects. Epo has been shown to improve cardiac contractility and endothelial function. Also, it releases young cells from the marrow that have a more favorable oxygen hemoglobin dissociation curve for tissue perfusion. In addition, Epo stimulates myocardial hypertrophy and is important for cardiac development in animals. This potential effect could be good or bad in humans, as most stimulants of myocardial growth increase apoptosis also. Clearly longer and larger trials need to be done before the Epo/iron approach to managing mild anemia in heart failure is embraced.
On the other hand, more attention to anemia in heart failure is clearly warranted based upon this study and others. Many large trials have shown a relationship between anemia and mortality in heart failure. Whether anemia is a marker for severe heart failure or a causally important aspect of severe heart failure is not completely clear, but this small study supports the latter. Transfusion is usually not recommended unless the patient is in severe heart failure and the Hgb is < 9 g%. Whether transfusion would be a viable option in the 9-12 Hgb range is unknown since there are definite risks both known and unknown with blood transfusion.
Although provocative and potentially important, there are significant limitations to this study. First, it is small (16 patients in each group). Thus, it is underpowered to look at mortality. Second, it is unblinded and the patients in the Epo/iron group clearly knew something was going on with all the injections they were getting. Thus, the potential for a substantial placebo effect is a concern. Third, 25% of the control group died, which complicates the analysis of the study parameters reported. Also, it is possible that all the deaths were in the control group by chance and their absence in the treatment group was not related to the interventions’ effect. Finally, the comorbid conditions in the 2 groups were similar, but not ideally matched, which is not surprising for such a small number of patients. For example, atrial fibrillation was 50% more frequent in the control group; hypertension was 40% more common in the controls; and idiopathic cardiomyopathy was twice as frequent in the control group. These differences could have influenced the results to favor the treatment group.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.