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Isosorbide Dinitrate plus Hydralazine for Blacks with Heart Failure

Add-on therapy worked well in this cohort of black patients who were receiving standard treatment.

The combination of hydralazine and isosorbide dinitrate was prescribed widely in the 1980s to treat heart failure, but its use declined in the 1990s when researchers showed angiotensin-converting-enzyme (ACE) inhibitors to be superior. However, retrospective analyses of clinical trials have suggested that black patients might be less responsive than white patients to ACE inhibitors. This observation prompted researchers to examine whether isosorbide plus hydralazine might be beneficial as add-on therapy for blacks with heart failure.

Researchers enrolled 1050 patients with advanced heart failure (mean ejection fraction, 24%) who identified themselves as black. Most already were receiving standard treatment, including ACE inhibitors and ß-blockers. The patients were randomized to receive either an isosorbide-hydralazine combination or placebo. The study was sponsored by a company that makes a fixed-dose combination tablet (not yet FDA-approved).

The trial was stopped after a mean follow-up of 10 months, when an interim analysis revealed significantly lower mortality with isosorbide-hydralazine than with placebo (6% vs. 10%). In addition, the isosorbide-hydralazine group experienced a significantly lower rate of hospitalization for heart failure (16% vs. 24%) and had a better mean quality-of-life score. Headache and dizziness were more common with active therapy than with placebo.

Comment: In this trial, isosorbide plus hydralazine was beneficial for black patients with heart failure who already were receiving standard therapy. The proposed mechanism is the creation of a more favorable balance between nitric oxide and superoxide production. However, an editorialist notes that these results do not exclude a benefit for other racial groups, and he discusses several problematic issues in "race-based therapeutics."

— Allan S. Brett, MD

Published in Journal Watch General Medicine November 30, 2004

Citation(s):

Taylor AL et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004 Nov 11; 351:2049-57.

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• Medline abstract (Free)

Hare JM. Nitroso-redox balance in the cardiovascular system. N Engl J Med 2004 Nov 11; 351:2112-4.

• Original article (Subscription may be required)
• Medline abstract (Free)

Bloche MG. Race-based therapeutics. N Engl J Med 2004 Nov 11; 351:2035-7.

• Original article (Subscription may be required)
• Medline abstract (Free)