title: Effectiveness of hydralazine/isosorbide dinitrate in racial/ethnic subgroups with heart failure.
abstract: BACKGROUND
  The addition of hydralazine/isosorbide dinitrate (H-ISDN) to a standard heart failure treatment regimen in the African-American Heart Failure Trial was associated with a 43% reduction in mortality. However, the effectiveness of H-ISDN in a community sample of African-American patients and other racial/ethnic groups is unknown.
  
  
  OBJECTIVE
  The aim of this study was to assess the associations between treatment with H-ISDN and mortality or hospitalization for heart failure in veterans with the disease.
  
  
  METHODS
  For this retrospective cohort study, electronic data on outpatient prescriptions, comorbidity, and other heart failure risk factors were analyzed in veterans with heart failure. Patients were classified based on whether they were prescribed H-ISDN and subclassified based on race/ethnicity (African American, Hispanic, or white). Patients who were prescribed H-ISDN were subclassified based on time of initiation of H-ISDN treatment (0-121, 122-365, or >365 days after diagnosis). Data were analyzed using propensity-adjusted Cox regression analyses, with exposure to H-ISDN modeled as a time-varying covariate.
  
  
  RESULTS
  Data from 76,828 veterans were analyzed (98% men, 2% women). H-ISDN prescription was not associated with the risk of death in 5 of the 9 subgroups predefined by race/ethnicity or time of initiation of H-ISDN; however, H-ISDN was associated with an increased risk of death in the 4 subgroups with longer times to initiation. H-ISDN was associated with a significantly increased risk of heart failure hospitalization in all but 1 of the 9 subgroups. The risk of both mortality and hospitalization associated with H-ISDN was significantly lower in African-American patients than in those who were Hispanic or white. Concurrent prescription of other, evidence-based heart failure therapies (eg, angiotensin-converting enzyme inhibitors, beta-blockers, and combinations) had strong, statistically significant associations with reduced mortality.
  
  
  CONCLUSIONS
  In this population of veterans with heart failure, H-ISDN prescription was not associated with significant reductions in mortality or hospitalization in any of the subgroups defined by race/ethnicity and time of initiation of H-ISDN analyzed compared with the group that did not receive H-ISDN. It is possible, or even likely, that unmeasured differences in important risk factors-particularly heart failure severity and left ventricular dysfunction-between the group that received H-ISDN and the one that did not masked a beneficial effect of H-ISDN. Therefore, our conclusions must be regarded as hypothesis generating and need to be tested in subsequent randomized trial(s).
authors.affiliation: Colorado Health Outcomes Program (F-443), University of Colorado at Denver, Denver, Colorado, USA. karl.hammermeister@uchsc.edu
authors.forename: Karl E
authors.initials: KE
authors.lastname: Hammermeister
authors.forename: Diane
authors.initials: D
authors.lastname: Fairclough
authors.forename: Caroline Bublitz
authors.initials: CB
authors.lastname: Emsermann
authors.forename: Richard
authors.initials: R
authors.lastname: Hamman
authors.forename: Michael
authors.initials: M
authors.lastname: Ho
authors.forename: Stephanie
authors.initials: S
authors.lastname: Phibbs
authors.forename: Mary
authors.initials: M
authors.lastname: Plomondon
authors.forename: Robert
authors.initials: R
authors.lastname: Valuck
authors.forename: David
authors.initials: D
authors.lastname: West
authors.forename: John F
authors.initials: JF
authors.lastname: Steiner
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D004338:Drug Combinations; D011307:Drug Prescriptions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000208:ethnology* / Q000401:mortality; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006760:Hospitalization; D006801:Humans; D006830:Hydralazine / Q000009:adverse effects / Q000627:therapeutic use*; D007548:Isosorbide Dinitrate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D018579:Patient Selection; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014728:Veterans; D044465:White People / Q000706:statistics & numerical data
chemical_list: D004338:Drug Combinations; D014665:Vasodilator Agents; C431665:isosorbide-hydralazine combination; D006830:Hydralazine; D007548:Isosorbide Dinitrate