The Use of EPO-Stimulating
Agents in Heart Failure
Nora Sharaya, PharmD
PGY2 Pharmacotherapy Resident
Butler 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
Functional
Iron
Deficiency
Hemodilution
Activation of
the
Inflammatory
Cascade
Anemia
Impaired EPO
Production
Concomitant
CKD
ISRN Hematol 2012; 2012: 246915
The Link Between Anemia and
Heart Failure
HF with
preserved EF
Anemia
HF with
unpreserved
EF
ISRN Hematol 2012; 2012: 246915
Mortality
 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
J Am Coll Cardiol. 2008;52:818–2.
Complications
Increased Risk of
Mortality
Reduced Exercise
Capacity
Impaired Quality
of Life
Increased Risk of
Hospitalization
J Am Coll Cardiol 2008;52:818–2
ACCF/AHA Guidelines
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
Circulation. 2013; 128: e240-e327.
Concerns with EPO Stimulating
Agents
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.”
Darbepoetin (Package Insert)
van Veldhuisen DJ, et al.
Study Design
Results
Applicability
• Randomized,
multinational,
double-blind,
placebo-controlled
• n=162 patients
In treated patients,
there were trends
towards
improvement in:
• Walking distance
• NYHA class
• Health-care
associated QOL
• Darbepoetin vs.
placebo trended
towards :
• Randomized to Wto  six-minute
based dose of SQ
walk distance
darbepoetin alfa, a
o Improvement
fixed dose, or
in NYHA class
placebo Q2W X25W
o Improvement
targeting Hgb 14.0
in health-care
associated QOL
• PO iron supplement
Eur Heart J. 2007;28:2208–16.
Ghali JK, et al.
Study Design
Results
• Randomized,
• n=162 (treatment)
multicenter,
• n=157 (placebo)
double blind,
• Mostly white males
placebo-controlled
with NHYA Class III
• Randomized to
HF
darbepoetin alfa
• Well-tolerated, but
(starting dose, 0.75
no increase in
ug/kg) or placebo
exercise tolerance
subcutaneously
Q2W for 52 weeks • A trend towards ↓
mortality and
hospitalization
Applicability
Darbepoetin is well
tolerated and
showed trends
towards
improvement:
• Exercise
tolerance
• Mortality
• Hospitalization
rate
Circulation. 2008;117:526–35.
Swedberg K, et al.
Study Design
• 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%
Results
Applicability
• n=1136 (treatment) • Do not support
• n=1142 (placebo)
the use of
darbepoetin to
• Primary composite
reduce the rate of
outcome:
hospitalization or
o Treatment: 576
death from any
(50.7%)
cause.
o Placebo: 565
(49.5%)
• Increased embolic
and thrombotic
events in the
treatment group
• A low hemoglobin
value may be a
marker of poor
prognosis versus a
treatment target
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, PharmD
PGY2 Pharmacotherapy Resident
Butler University & Community Health Network
Email: nsharaya2@ecommunity.com