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)

• Published in: The American journal of cardiology 2007-08, Vol.100 (4), p.684-689
• Main Authors: Yancy, Clyde W., MD, Ghali, Jalal K., MD, Braman, Virginia M, Sabolinski, Michael L., MD, Worcel, Manuel, MD, Archambault, W. Tad, PhD, Franciosa, Joseph A., MD
• Format: Article
• Language: English
• Subjects: Administration, Oral; African Americans; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug dosages; Drug therapy; Female; Follow-Up Studies; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - ethnology; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Hydralazine - administration & dosage; Isosorbide Dinitrate - administration & dosage; Male; Medical sciences; Middle Aged; Mortality; Patient Compliance; Patient safety; Prescription drugs; Quality of Life; Stroke Volume - drug effects; Survival Rate; Treatment Outcome; United States - epidemiology
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2007.03.086

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 ≥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.