Influence of blood pressure on the effectiveness of a fixed-dose combination of isosorbide dinitrate and hydralazine in the African-American Heart Failure Trial.
OBJECTIVE
This study sought to assess the effect of baseline systolic blood pressure (SBP) and changes in SBP on the effectiveness of treatment with fixed-dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in patients with heart failure (HF).


BACKGROUND
Low SBP is a risk factor for adverse outcomes in patients with HF. However, FDC I/H lowered SBP in the A-HeFT (African-American Heart Failure Trial) and yet prolonged survival. Whether blood pressure (BP) lowering is critical to the efficacy of FDC I/H and whether a low BP limits its effectiveness is unclear.


METHODS
The effects of FDC I/H on SBP and on mortality and hospitalization were compared in patients with a low or high baseline SBP using multivariable Cox regression models. The interaction between the effect of treatment and baseline SBP was examined.


RESULTS
Mean +/- SD baseline SBP in all of the patients was 126 +/- 18 mm Hg. Patients with baseline SBP equal to or below the median (126 mm Hg) had features of more severe HF. Baseline SBP equal to or below the median was an independent risk factor for death (hazard ratio [HR] 2.09; 95% confidence interval [CI] 1.02 to 4.29) or first hospitalization for HF (HR 1.66; 95% CI 1.18 to 2.34). The FDC I/H treatment reduced BP in patients with SBP above the median but not in patients with SBP below 126 mm Hg. The FDC I/H treatment was associated with a similar decrease in mortality or hospitalization for HF in patients with SBP below the median and above the median. The effects of FDC I/H on mortality alone were also similar.


CONCLUSIONS
In A-HeFT, patients with lower SBP had a greater risk but a similar relative benefit from the use of FDC I/H as those with higher SBP. The FDC I/H treatment did not reduce SBP in patients with low SBP. An asymptomatic low SBP should not be considered a contraindication to use of FDC I/H in patients with HF.
Anand
Inder S
IS
VA Medical Center, Minneapolis, Minnesota, USA. anand001@umn.edu
Tam
S William
SW
Rector
Thomas S
TS
Taylor
Anne L
AL
Sabolinski
Michael L
ML
Archambault
W Tad
WT
Adams
Kirkwood F
KF
Olukotun
Adeoye Y
AY
Worcel
Manuel
M
Cohn
Jay N
JN
D000328:Adult; D001741:Black or African American; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D015897:Comorbidity; D004338:Drug Combinations; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D006830:Hydralazine / Q000627:therapeutic use*; D007022:Hypotension / Q000453:epidemiology; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013599:Systole; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
D000959:Antihypertensive Agents; D004338:Drug Combinations; D014665:Vasodilator Agents; D006830:Hydralazine; D007548:Isosorbide Dinitrate