Accepted Manuscript Clinical Outcomes of Erythropoietin Use in Heart Failure Patients with Anemia of Chronic Kidney Disease Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS Cindy Shutieng Fan, PharmD Alberta Warner, MD PII:
S1071-9164(14)00064-5
DOI:
10.1016/j.cardfail.2014.02.001
Reference:
YJCAF 3258
To appear in:
Journal of Cardiac Failure
Received Date: 18 July 2013 Revised Date:
5 February 2014
Accepted Date: 6 February 2014
Please cite this article as: Jackevicius C, Fan CS, Warner A, Clinical Outcomes of Erythropoietin Use in Heart Failure Patients with Anemia of Chronic Kidney Disease, Journal of Cardiac Failure (2014), doi: 10.1016/j.cardfail.2014.02.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Clinical Outcomes of Erythropoietin Use in Heart Failure Patients with Anemia of Chronic Kidney Disease
RI PT
Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS,1-5 Cindy Shutieng Fan, PharmD,1,2 Alberta Warner, MD2,6
College of Pharmacy, Western University of Health Sciences, 2VA Greater Los Angeles
SC
1
Healthcare System, 3Institute for Clinical Evaluative Sciences, 4Institute for Health Policy,
M AN U
Management and Evaluation, 5University Health Network, 6Department of Medicine, Division of Cardiology, UCLA
TE D
Address for correspondence:
Cynthia Jackevicius, BScPhm, PharmD, MSc, FCSHP, BCPS, AQ Cardiology Professor, College of Pharmacy, Western University of Health Sciences
EP
309 E. Second St., Pomona CA 91766;
AC C
Phone: 909-469-5527; Fax: 909-469-5539; [email protected]
Running title: Outcomes of EPO in CRAS
This study was funded by the American College of Clinical Pharmacy Watson Anemia Investigator Development Research Award.
1
ACCEPTED MANUSCRIPT
Abstract Background: Anemia and chronic kidney disease are common disorders in heart failure (HF) patients, and are associated with increased morbidity and mortality. This study assesses clinical
RI PT
outcomes associated with erythropoietin (EPO) treatment in this cardio-renal-anemia syndrome (CRAS) population.
Methods and Results: This is a retrospective cohort study of VA patients with CRAS from
SC
January 2003 to December 2006. The primary outcome was a composite of death, acute coronary syndromes, HF and stroke. Multiple Cox regression modeling was used to evaluate the outcome
M AN U
in patients prescribed (n=213) and not prescribed EPO (n=1845). Adjusted incidence of mortality was statistically significantly higher in EPO than non-EPO users (33.8% vs. 19.7%;HR:1.40 95%CI1.06-1.85, p=0.02). The unadjusted composite of cardiovascular events/death was higher in the EPO group, but not statistically significant when adjusted for confounders (p=0.12). Crude
TE D
ACS events were documented in 18.8% and 10.8% patients (p=0.001), and stroke events occurred in 22.5% and 18.3% patients (p=0.14) in EPO and non-EPO groups, respectively. Conclusions: We found that in CRAS patients, EPO use was associated with increased risk of
EP
mortality and a trend towards increased cardiovascular events. Therefore, clinicians considering
use.
AC C
EPO use in CRAS patients should assess whether any potential benefits outweigh the risks of
Key Words: cardiac, health policy, outcome research
2
ACCEPTED MANUSCRIPT
Introduction Despite advances in therapy, heart failure (HF), a common and progressive condition, continues to be associated with a substantial increase in morbidity and mortality.1-3 The majority
RI PT
of patients with HF also have comorbidities, such as, hypertension, diabetes, dyslipidemia and coronary artery disease. Treatment used for HF and these comorbidities may contribute to the development of chronic kidney disease (CKD) if cardiac output is decreased, with such patients
complicate management of the other condition.
SC
progressing to end-stage renal disease.4 Depending on the severity, both HF and CKD can
M AN U
Anemia is also a common complication that is observed in both CKD and HF.1-3,5 The prevalence of anemia in HF patients range from 7-70% depending on the patient cohort, and increases as HF severity worsens.2,4-8 In the OPTIMIZE-HF registry, 51.2% of patients hospitalized for HF had hemoglobin levels of
S1071-9164(14)00064-5
DOI:
10.1016/j.cardfail.2014.02.001
Reference:
YJCAF 3258
To appear in:
Journal of Cardiac Failure
Received Date: 18 July 2013 Revised Date:
5 February 2014
Accepted Date: 6 February 2014
Please cite this article as: Jackevicius C, Fan CS, Warner A, Clinical Outcomes of Erythropoietin Use in Heart Failure Patients with Anemia of Chronic Kidney Disease, Journal of Cardiac Failure (2014), doi: 10.1016/j.cardfail.2014.02.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Clinical Outcomes of Erythropoietin Use in Heart Failure Patients with Anemia of Chronic Kidney Disease
RI PT
Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS,1-5 Cindy Shutieng Fan, PharmD,1,2 Alberta Warner, MD2,6
College of Pharmacy, Western University of Health Sciences, 2VA Greater Los Angeles
SC
1
Healthcare System, 3Institute for Clinical Evaluative Sciences, 4Institute for Health Policy,
M AN U
Management and Evaluation, 5University Health Network, 6Department of Medicine, Division of Cardiology, UCLA
TE D
Address for correspondence:
Cynthia Jackevicius, BScPhm, PharmD, MSc, FCSHP, BCPS, AQ Cardiology Professor, College of Pharmacy, Western University of Health Sciences
EP
309 E. Second St., Pomona CA 91766;
AC C
Phone: 909-469-5527; Fax: 909-469-5539; [email protected]
Running title: Outcomes of EPO in CRAS
This study was funded by the American College of Clinical Pharmacy Watson Anemia Investigator Development Research Award.
1
ACCEPTED MANUSCRIPT
Abstract Background: Anemia and chronic kidney disease are common disorders in heart failure (HF) patients, and are associated with increased morbidity and mortality. This study assesses clinical
RI PT
outcomes associated with erythropoietin (EPO) treatment in this cardio-renal-anemia syndrome (CRAS) population.
Methods and Results: This is a retrospective cohort study of VA patients with CRAS from
SC
January 2003 to December 2006. The primary outcome was a composite of death, acute coronary syndromes, HF and stroke. Multiple Cox regression modeling was used to evaluate the outcome
M AN U
in patients prescribed (n=213) and not prescribed EPO (n=1845). Adjusted incidence of mortality was statistically significantly higher in EPO than non-EPO users (33.8% vs. 19.7%;HR:1.40 95%CI1.06-1.85, p=0.02). The unadjusted composite of cardiovascular events/death was higher in the EPO group, but not statistically significant when adjusted for confounders (p=0.12). Crude
TE D
ACS events were documented in 18.8% and 10.8% patients (p=0.001), and stroke events occurred in 22.5% and 18.3% patients (p=0.14) in EPO and non-EPO groups, respectively. Conclusions: We found that in CRAS patients, EPO use was associated with increased risk of
EP
mortality and a trend towards increased cardiovascular events. Therefore, clinicians considering
use.
AC C
EPO use in CRAS patients should assess whether any potential benefits outweigh the risks of
Key Words: cardiac, health policy, outcome research
2
ACCEPTED MANUSCRIPT
Introduction Despite advances in therapy, heart failure (HF), a common and progressive condition, continues to be associated with a substantial increase in morbidity and mortality.1-3 The majority
RI PT
of patients with HF also have comorbidities, such as, hypertension, diabetes, dyslipidemia and coronary artery disease. Treatment used for HF and these comorbidities may contribute to the development of chronic kidney disease (CKD) if cardiac output is decreased, with such patients
complicate management of the other condition.
SC
progressing to end-stage renal disease.4 Depending on the severity, both HF and CKD can
M AN U
Anemia is also a common complication that is observed in both CKD and HF.1-3,5 The prevalence of anemia in HF patients range from 7-70% depending on the patient cohort, and increases as HF severity worsens.2,4-8 In the OPTIMIZE-HF registry, 51.2% of patients hospitalized for HF had hemoglobin levels of
