Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial.
BACKGROUND
We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality.


RESULTS
Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at approximately 50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012).


CONCLUSIONS
FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.
Taylor
Anne L
AL
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Ziesche
Susan
S
Yancy
Clyde W
CW
Carson
Peter
P
Ferdinand
Keith
K
Taylor
Malcolm
M
Adams
Kirkwood
K
Olukotun
Adeoye Y
AY
Ofili
Elizabeth
E
Tam
S William
SW
Sabolinski
Michael L
ML
Worcel
Manuel
M
Cohn
Jay N
JN
D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D018771:Arthralgia / Q000139:chemically induced; D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002423:Cause of Death; D018572:Disease-Free Survival; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004338:Drug Combinations; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000523:psychology; D016027:Heart Transplantation / Q000706:statistics & numerical data; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage / Q000627:therapeutic use*; D007022:Hypotension / Q000139:chemically induced; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011788:Quality of Life; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D015415:Biomarkers; D002317:Cardiovascular Agents; D004338:Drug Combinations; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D006830:Hydralazine; D007548:Isosorbide Dinitrate