PMID- 18041162
OWN - NLM
STAT- MEDLINE
DCOM- 20080401
LR  - 20221207
IS  - 1175-3277 (Print)
IS  - 1175-3277 (Linking)
VI  - 7
IP  - 5
DP  - 2007
TI  - Effects of ACE inhibitors or beta-blockers in patients treated with the 
      fixed-dose combination of isosorbide dinitrate/hydralazine in the 
      African-American Heart Failure Trial.
PG  - 373-80
AB  - BACKGROUND: In the A-HeFT (African-American Heart Failure Trial), treatment of 
      African-American patients with New York Heart Association (NYHA) class III/IV 
      heart failure (HF) with fixed-dose combination (FDC) of isosorbide 
      dinitrate/hydralazine (I/H) reduced mortality and morbidity and improved patient 
      reported functional status compared with standard therapy alone. OBJECTIVE: To 
      examine the benefit of FDC I/H in subgroups based on baseline drug therapy and to 
      investigate whether ACE inhibitors and/or angiotensin receptor antagonists 
      (angiotensin receptor blockers) [ARBs] or beta-adrenoceptor antagonists 
      (beta-blockers) provided additional benefit in FDC I/H-treated African-American 
      patients with HF. STUDY DESIGN: The A-HeFT was a double-blind, placebo-controlled 
      study enrolling 1050 patients stabilized on optimal HF therapies and with NYHA 
      class III/IV HF with systolic dysfunction conducted during the years 2001-4 with 
      up to 18 months follow-up. The primary endpoint was a composite of mortality, 
      first HF hospitalization, and improvement of quality of life at 6 months. 
      Secondary endpoints included mortality, hospitalizations, and change in quality 
      of life. Prospective Kaplan-Meier survival analyses were used for differences 
      between FDC I/H and placebo groups and retrospective analyses were conducted 
      within FDC I/H-treated and placebo groups. RESULTS: Subgroup analysis for 
      mortality, event-free survival (death or first HF hospitalization), and HF 
      hospitalization showed that FDC I/H, compared with placebo, was effective with or 
      without ACE inhibitors or beta-blockers or other standard medications with 
      all-point estimates favoring the FDC I/H group. Within the placebo-treated group, 
      beta-blockers or ACE inhibitors and/or ARBs were efficacious in improving 
      survival (hazard ratio [HR] 0.33; p<0.0001 for [beta]-blocker use and HR 0.39; 
      p=0.01 for ACE inhibitor and/or ARB use). However, within the FDC I/H-treated 
      group, use of beta-blockers, but not ACE inhibitors and/or ARBs, provided 
      additional significant benefit for survival (HR 0.44; p=0.029 and HR 0.60; 
      p=0.34, respectively), event-free survival (HR 0.62; p=0.034 and HR 0.72; p=0.29, 
      respectively) and the composite score of death, HF hospitalization and change in 
      quality of life (p=0.016 and p=0.13, respectively). CONCLUSION: Based on the 
      analysis of baseline medication use in the A-HeFT, FDC I/H was superior to 
      placebo with or without beta-blockers or ACE inhibitor. However, beta-blockers 
      but not ACE inhibitors and/or ARBs provided additional significant benefit in 
      African-Americans with HF treated with FDC I/H. These analyses are hypotheses 
      generating and their confirmation in clinical trials needs to be considered.
FAU - Ghali, Jalal K
AU  - Ghali JK
AD  - University Health Center, Wayne State University, Detroit, MI 48201, USA. 
      jghali@med.wayne.edu
FAU - Tam, S William
AU  - Tam SW
FAU - Ferdinand, Keith C
AU  - Ferdinand KC
FAU - Lindenfeld, JoAnn
AU  - Lindenfeld J
FAU - Sabolinski, Michael L
AU  - Sabolinski ML
FAU - Taylor, Anne L
AU  - Taylor AL
FAU - Worcel, Manuel
AU  - Worcel M
FAU - Curry, Charles L
AU  - Curry CL
FAU - Cohn, Jay N
AU  - Cohn JN
CN  - A-HeFT Investigators
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Vasodilator Agents)
RN  - 26NAK24LS8 (Hydralazine)
RN  - IA7306519N (Isosorbide Dinitrate)
SB  - IM
MH  - Adrenergic beta-Antagonists/*therapeutic use
MH  - *Black or African American
MH  - Angiotensin Receptor Antagonists
MH  - Angiotensin-Converting Enzyme Inhibitors/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Female
MH  - Heart Failure/*drug therapy/ethnology
MH  - Humans
MH  - Hydralazine/*therapeutic use
MH  - Isosorbide Dinitrate/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Treatment Outcome
MH  - Vasodilator Agents/*therapeutic use
EDAT- 2007/11/29 09:00
MHDA- 2008/04/02 09:00
CRDT- 2007/11/29 09:00
PHST- 2007/11/29 09:00 [pubmed]
PHST- 2008/04/02 09:00 [medline]
PHST- 2007/11/29 09:00 [entrez]
AID - 10.2165/00129784-200707050-00007 [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2007;7(5):373-80. doi: 10.2165/00129784-200707050-00007.