|Year : 2018 | Volume
| Issue : 2 | Page : 78
Targeting anemia in heart failure
Rakesh Agarwal MBBS, MD
Department of Cardiology, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
|Date of Web Publication||23-Mar-2018|
Dr. Rakesh Agarwal
IPGMER and SSKM Hospital, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Agarwal R. Targeting anemia in heart failure. J Clin Prev Cardiol 2018;7:78
Iron deficiency (ID) affects up to 50% heart failure (HF) patients and leads to poor quality of life (QoL), impaired exercise tolerance, and mortality. Yet, this important aspect of care has received little attention in HF patients.
Trials have generally used definitions of Iron Deficiency (ID) as ferritin <100 mcg/L or 100–300 mcg/L with transferrin saturation (TSAT) <20%. ID, thus defined, is present in 37% of patients with stable systolic HF and is more prevalent in women.
Erythropoietin-stimulating agents have been associated with increased risk of thromboembolic phenomena and may increase blood pressure, activate thrombogenesis, and cause vascular injury by several mechanisms involving prostaglandin, endothelin, and renin-angiotensin systems. The “Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure” trial found a significant increase in thromboembolic events among patients receiving darbepoetin alfa with no reduction of death or hospitalization rates in patients with systolic HF.
Some major studies have evaluated the role of intravenous (IV) iron therapy in patients with systolic HF. The FERRIC-HF trial assigned patients to receive 16 weeks of IV iron sucrose or placebo. There was no significant improvement in Hemoglobin Hb levels. Yet, there was a trend toward improved exercise tolerance and increased exercise duration and significant improvement in New York Heart Association (NYHA) class, patient global assessment (PGA), and fatigue score. This suggests that the improvement in congestive HF was at least partially due to corrected iron levels and not an increase in Hb only.
The Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency (FAIR-HF) trial showed that compared to placebo, patients receiving IV iron ferric carboxymaltose (FCM) had improved PGA, NYHA functional class, QoL, and 6-min walk test (6MWT) scores. These benefits were similar in groups with Hb levels ≤12 or >12 g/dL with a similar death and adverse event rate in both groups.
The Ferric CarboxymaltOse evaluatioN on perFormance in patients with IRon deficiency in combination with chronic Heart Failure (CONFIRM-HF) trial enrolled patients with Hb <15 g/dL, reduced left ventricular ejection fraction and ID. Treatment with IV iron FCM led to sustainable improvement in functional capacity as measured by 6MWT, reduced risk of hospital admission due to worsening HF during 1-year follow-up, and improved QoL. No severe allergic reactions to iron were reported.
The IRONOUT-HF trial failed to show significant differences between groups receiving either oral iron polysaccharide 150 mg twice daily or placebo for 16 weeks, with relation to peak VO2, 6MWT, QoL, or NT-pro B-type natriuretic peptide levels.
Oral salts are also plagued with problems related to the gastrointestinal side effects and poor compliance. Absorption is delayed or hampered by many foods and medications. Intestinal edema in HF patients may further lead to unpredictable absorption. Further upregulation of hepcidin impairs dietary absorption of iron in HF patients.
In retrospect, we can conclude that the trials have demonstrated that IV iron is a safe and beneficial therapy in patients with ID and systolic HF. This benefit is at least partially independent of Hb levels. This benefit translates clinically into improved QoL, improved physical activity, and reduced hospitalization rates. Oral iron therapy, however, is not an effective alternative to IV therapy in HF patients with ID. Erythropoiesis-stimulating agents are best avoided.
However, there are some inherent difficulties raised with these assumptions. ID levels used in trials are ill-defined. The combination of a ferritin >100 mcg/L and TSAT <20% is highly suggestive of the anemia of inflammation rather than absolute ID. Second, overcorrection with iron therapy may be harmful with its proinflammatory effects. Third, no proper assays are available to predict either response to IV iron or its deficiency. Treatment of nonanemic ID may seem attractive on paper, but the number of clinicians prepared to do so is difficult to assess. Finally, the role of iron therapy in similar patients with HF with preserved EF remains to be defined. We can only wait before longer studies and trials addressing these questions become available.
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Conflicts of interest
There are no conflicts of interest.