Use of Hydralazine-Isosorbide Dinitrate combination in African American and Other Race/Ethnic Group Patients with Heart Failure and Reduced Ejection Fraction

Harsh Golwala, MD;1 Udho Thadani, MD;1 Li Lang, MD, PhD;2 Stavros Stavrakis, MD, PhD;1 Javed Butler MD;3 Clyde W. Yancy, MD;4 Deepak L. Bhatt, MD, MPH;5 Adrian Hernandez, MD, MHS;2 Gregg C. Fonarow, MD6

1University of Oklahoma, Oklahoma City, OK; 2Duke Clinical Research Institute, Durham, NC; 3Emory University, Atlanta, GA; 4Northwestern University, Chicago, IL; 5VA Boston Healthcare System, Brigham and Women’s Hospital, Boston, MA; 6UCLA Medical Center, Los Angeles, CA

Results ACC/AHA and HFSA guidelines recommend the use of

Hydralazine-Isosorbide Dinitrate (H-ISDN) in self identified African American patients with heart failure and reduced ejection fraction (HFrEF). In addition, H-ISDN may be considered in non-African American patients with HFrEF who remains symptomatic on optimized standard therapy.

Background

To determine the contemporary use of H-ISDN use over time in both African American and other racial/ethnic groups, trends in its use over time, as well as patient and hospital factors associated with its use.

Objective

Methods

Conclusions

Limitations

GWTG-HF is an ongoing, prospective registry and quality improvement program initiated in January 2005 by the American Heart Association (AHA)

122,395 patients admitted with HF were discharged from 207 hospitals participating in GWTG-HF program from April 1, 2008 through March 24, 2012.

Of these, patients with missing data on ejection fraction [n=3,868] or ejection fraction >40% [n=63,905] were excluded yielding a population of 54,622 HFrEF patients.

Further exclusions included unknown race or ethnicity [n=2,288], and documented contra-indication to H-ISDN therapy [n=2,508]. We also excluded patients who were comfort care only, or those who died, or who had missing information on discharge destination.

The final study population thus included 43,898 patients with HFrEF from 195 hospitals

Outcomes Sciences, a Quintiles Company, Cambridge, MA served as the data collection center and Duke Clinical Research Institute served as the data analysis center.

The data collection is dependent on the accuracy and completeness of data abstraction.

Measured and unmeasured confounding factors may impact findings.

Data do not include longitudinal follow-up, hence a portion of eligible patients may have been started on H-ISDN as an outpatient, underestimating its real use. However, previous data suggest that if a medication is not started at the time of discharge; subsequent new prescription rate in outpatient setting is low.

Finally, GWTG-HF hospitals are self-selected and may not be representative to all hospitals in the US.

Hydralazine-isosorbide dinitrate use in eligible African American patients with HFrEF remains very low in real world practice despite clinical trial evidence and guideline recommendations.

Although H-ISDN use has increased over time from 2008 through 2011, it has nevertheless remained less than 25% even in the African American patients.

Given the substantial morbidity and mortality faced by patients with HFrEF and the established efficacy of H-ISDN among African American patients, aggressive measures to facilitate adherence to H-ISDN should be sought.

Table 1.Patient Characteristics by Hydralazine-Isosorbide Dinitrate Use at Hospital Discharge

Figure 1. Current Use as Well as Trends in the Use of Hydralazine-isosorbide Dinitrate at Discharge in Eligible Patients from 2008-2011

Table 2. Patient and Hospital Factors Associated with H-ISDN Use in Self-Identified African American Patients

Figure 2. H-ISDN Use in African American Patients in Hospitals with at Least 10 Self-Identified African American Patients

Hydralazine-Isosorbide dintrate use No. (%)

Patient characteristics Total (n=43,898)

Yes(n=5,515)

No(n=38,383)

P value

Age, mean (SD), y 68.3 (15) 65.4 (15) 68.7 (15) <.0001Male (%) 62.4 65.8 61.9 <.0001Race (Median) White 61.3 43.6 63.8

<.001 African American 25.4 45.3 22.6 Hispanic 8.7 7.5 8.8 Others 4.4 3.4 4.62Hypertension (%) 74.2 82.1 73.1 <.0001Diabetes (%) 41.2 50.5 39.9 <.0001Hyperlipidemia (%) 48.2 50.1 47.9 0.003Atrial Fibrillation (%) 29.9 26.3 30.4 <.0001COPD (%) 27.6 29.0 27.4 0.018Peripheral vascular disease (%) 11.6 13.6 11.3 <.0001Coronary artery disease (%) 50.9 52.1 50.7 0.05CVA (%) 13.4 16.0 13.1 <.0001ICD (%) 19.6 25.3 18.8 <.0001Heart failure (%) 73.2 79.5 72.3 <.0001Pacemaker (%) 14.3 13.5 14.4 0.08CRT-P (%) 0.8 0.8 0.8 0.64CRT-D (%) 8.8 12.1 8.3 <.0001Chronic dialysis (%) 2.9 3.9 2.8 <.0001Smoking (%) 21.8 22.0 21.81 0.78Ejection fraction, mean (SD) 24.7 (7.8) 24.8 (7.8) 24.7 (7.8) 0.31

All values listed as mean ± standard deviation or %.Wilcoxon two-sample test performed for continuous variables.Chi-square test performed for categorical variables.Abbreviations: COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; ICD, Implantable cardioverter defibrillator; CRT- D,P= Cardiac resynchronization therapy- pacemaker, defibrillator

Variable Adjusted OR P value

Age, per 10 y 0.90 (0.86-0.95) <0.001

Female vs. Male 0.76 (0.68-0.85) <0.001Uninsured vs Medicare 0.82 (0.70-0.76) 0.0118COPD 1.19 (1.07-1.31) 0.001Diabetes 1.20 (1.07-1.35) 0.0025Hypertension 1.30 (1.07-1.58) 0.0084ICD implantation 1.36 (1.19-1.55) <0.0001Heart Failure 1.39 (1.23-1.58) <0.0001Anemia 1.27 (1.07-1.50) 0.0052Chronic dialysis 0.59 (0.42-0.83) 0.0028Renal insufficiency 2.33 (2.01-2.69) <0.0001Smoking 0.82 (0.72-0.93) 0.0026Systolic BP. Per 10 mm Hg 1.15 (1.12-1.18) <0.0001Heart rate, per 10 beats/min 0.93 (0.91-0.95) <0.0001Hospital Bed size, per 500 beds 1.77 (1.24-2.52) 0.0018

Abbreviations: COPD, chronic obstructive pulmonary disease; ICD, implantable cardioverter defibrillator

Race % of patients with H-ISDN discharge

African American 22.3

White 8.9

Hispanics 10.8

Others 9.8

Disclosures: GWTG-HF program is provided by the AHA.GWTG-HF has been funded in the past through support from Medtronic, GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. This project was also supported by Young Investigator Database Research Seed Grant to Dr. Golwala -supported by the Council on Clinical Cardiology.