Evidence for the continued safety and tolerability of fixed-dose isosorbide dinitrate/hydralazine in patients with chronic heart failure (the extension to African-American Heart Failure Trial).
The benefits of fixed-dose combination isosorbide dinitrate plus hydralazine (ID/H) in African-Americans with heart failure (HF) were established by the African-American Heart Failure Trial (A-HeFT), which was terminated early because of a significant survival benefit of ID/H. The Extension to A-HeFT trial (X-A-HeFT), designed to make ID/H available for ethical reasons after A-HeFT termination, afforded an opportunity to further observe responsiveness and compliance with ID/H. In total 198 patients completing the A-HeFT took ID/H for an additional 209 +/- 116 days. Their age (57 +/- 13 years), cause and duration of HF, and HF medications were not different from all A-HeFT patients. New York Heart Association class at X-A-HeFT baseline was > or =III in 51% of patients versus 100% of all patients at A-HeFT baseline, remained unchanged in most patients, improved in 24%, and worsened in only 9% during X-A-HeFT. The average number of ID/H tablets taken during X-A-HeFT was 3.7 +/- 1.8 per day with compliance averaging 87 +/- 25%. The most common adverse events, headache (34%) and dizziness (16%), were less than in patients taking ID/H in A-HeFT, with only 6% discontinuations for adverse events. The 6% annualized mortality rate in X-A-HeFT was the same as for ID/H in A-HeFT. There were no statistically significant differences in baseline characteristics or outcomes in X-A-HeFT patients analyzed according to their A-HeFT randomization. In conclusion, these results confirm the good compliance, tolerability, and responsiveness, with low mortality and improved symptoms, during treatment with ID/H observed in A-HeFT.
Yancy
Clyde W
CW
Baylor University Medical Center, Heart and Vascular Institute, Dallas, Texas, USA.
Ghali
Jalal K
JK
Braman
Virginia M
VM
Sabolinski
Michael L
ML
Worcel
Manuel
M
Archambault
W Tad
WT
Franciosa
Joseph A
JA
D000284:Administration, Oral; D001741:Black or African American; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage*; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011788:Quality of Life; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D004338:Drug Combinations; C431665:isosorbide-hydralazine combination; D006830:Hydralazine; D007548:Isosorbide Dinitrate