The response to therapy with a fixed dose combination of isosorbide dinitrate and hydralazine (FDC I/H) is enhanced in African Americans with heart failure and reduced ejection fraction (HFrEF) when compared to similar white cohorts. This study will seek to confirm the previous genetic sub-study from AHeFT which suggested a functional polymorphism of guanine nucleotide binding protein beta polypeptide 3 subunit (GNB3), C825T in exon 10, influences the therapeutic efficacy of FDC I/H. This study will initiate treatment with FDC I/H in 500 self designated African American subjects with systolic heart failure. They will be followed for up to two years on therapy. Clinical outcomes (survival, heart failure hospitalizations, and change in quality of life) on FDC I/H will be compared by GNB3 genotype subset. The hypothesis to be confirmed is that subjects homozygous for the T allele (those with the GNB3 TT genotype which is present in approximately 50% of black subjects) demonstrate enhanced therapeutic benefit from FDC I/H.
Name: FDC I/H
Description: All subjects in both groups will be initiated on drug, FDC I/H with dose titrated up to target doses based on clinical guidelinesType: DrugGNB3 TT GNB3 C
Description: The CS combines three outcome variables into a single "score". Composite score adds points for survival over 2 years of follow up (death at any time yields -3 points, survival to end of study results in 0), heart failure hospitalization over 2 years of follow up (yes at any time results in -1 point, no results in 0), and the change in the raw quality of life score on the Minnesota Living with Heart Failure Questionnaire from entry to 6 months (change of ten units or greater=increase +2, decrease-2; change 5 to 9= increase+1, decrease -1; change < 5 units for the raw score yields 0 points). The CS will range from -6 to +2 for each patient.
Measure: Composite score (CS) no units. (survival, heart failure hospitalization, and change in the raw quality of life score on the Minnesota Living with Heart Failure Questionnaire) Time: 2 yearsDescription: Comparison of survival on therapy by GNB3 genotype
Measure: Survival Time: 2 yearsDescription: Comparison of event free survival by GNB3 genotype.
Measure: Survival free from heart failure hospitalization Time: 2 yearsDescription: Evaluate the change in the raw score of the Quality of Life questionnaire by GNB3 genotype.
Measure: Change in Quality of Life Assessment by Minnesota Living with Heart Failure Questionnaire Time: 6 monthsCohort
There is one SNP
This study will seek to confirm the previous genetic sub-study from AHeFT which suggested a functional polymorphism of guanine nucleotide binding protein beta polypeptide 3 subunit (GNB3), C825T in exon 10, influences the therapeutic efficacy of FDC I/H. --- C825T ---