The Use of EPO-Stimulating Agents in Heart Failure
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The Use of EPO-Stimulating Agents in Heart Failure
Nora Sharaya, PharmDPGY2 Pharmacotherapy ResidentButler University & Community Health Network
This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation
The Link Between Anemia and Heart Failure
AnemiaHemodilution
Functional Iron
Deficiency
Activation of the
Inflammatory Cascade
Impaired EPO Production
Concomitant CKD
ISRN Hematol 2012; 2012: 246915
HF with preserved EF
HF with unpreserved
EF
Anemia
The Link Between Anemia and Heart Failure
ISRN Hematol 2012; 2012: 246915
A meta-analysis published in 2008 examined 153,180 patients with chronic heart failure Of those patients, 37.2% were anemic
After a minimum of six months follow up, 46.8% of patients with anemia died compared to 29.5% of the patients without anemia Based on these results, in patients without an identifiable
cause for their anemia, using erythropoietin-stimulating agents has been considered
Mortality
J Am Coll Cardiol. 2008;52:818–2.
Increased Risk of Mortality
Reduced Exercise Capacity
Impaired Quality of Life
Increased Risk of Hospitalization
Complications
J Am Coll Cardiol 2008;52:818–2
Acknowledge the link between anemia and heart failure• Discuss associated complications
No cited recommendation on use of EPO stimulating agents for treatment• Lack of definitive evidence
ACCF/AHA Guidelines
Circulation. 2013; 128: e240-e327.
US Boxed Warning:
“Erythropoiesis-stimulating agents (ESAs) increased the risk of serious cardiovascular events, thromboembolic events, stroke, and mortality in clinical studies when administered to target hemoglobin levels >11 g/dL.”
Concerns with EPO Stimulating Agents
Darbepoetin (Package Insert)
van Veldhuisen DJ, et al.
Study Design Results Applicability
• Randomized, multinational, double-blind, placebo-controlled
• Randomized to Wt-based dose of SQ darbepoetin alfa, a fixed dose, or placebo Q2W X25W targeting Hgb 14.0
• PO iron supplement
• n=162 patients • Darbepoetin vs.
placebo trended towards :o six-minute
walk distanceo Improvement
in NYHA classo Improvement
in health-care associated QOL
In treated patients, there were trends towards improvement in:• Walking distance • NYHA class• Health-care
associated QOL
Eur Heart J. 2007;28:2208–16.
Ghali JK, et al.
Study Design Results Applicability
• Randomized, multicenter, double blind, placebo-controlled
• Randomized to darbepoetin alfa (starting dose, 0.75 ug/kg) or placebo subcutaneously Q2W for 52 weeks
• n=162 (treatment)• n=157 (placebo) • Mostly white males
with NHYA Class III HF
• Well-tolerated, but no increase in exercise tolerance
• A trend towards ↓ mortality and hospitalization
Darbepoetin is well tolerated and showed trends towards improvement:• Exercise
tolerance• Mortality• Hospitalization
rate
Circulation. 2008;117:526–35.
Study Design Results Applicability • Randomized,
double-blind, multinational, placebo-controlled
• Randomized to darbepoetin alfa 0.75 ug/kg (titrate to Hg>13.0) or placebo SQ Q2W
• Iron therapy given if TSAT <20%
• n=1136 (treatment)• n=1142 (placebo)• Primary composite
outcome:o Treatment: 576
(50.7%) o Placebo: 565
(49.5%)• Increased embolic
and thrombotic events in the treatment group
• Do not support the use of darbepoetin to reduce the rate of hospitalization or death from any cause.
• A low hemoglobin value may be a marker of poor prognosis versus a treatment target
Swedberg K, et al.
N Engl J Med. 2013;368:1210–19.
Conclusions
Treatment Target
Poor Prognostic Sign
The Use of EPO-Stimulating Agents in Heart Failure
Nora Sharaya, PharmDPGY2 Pharmacotherapy ResidentButler University & Community Health NetworkEmail: [email protected]