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: nsharaya2@ecommunity.com