Taylor AL, Ziesche S, Yancy C, et al: Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351(20):2049-57.
Hare JM: Nitroso-redox balance in the cardiovascular system. N Engl J Med 2004;351(20):2112-14(editorial).
Bloche MG: Race-based therapeutics. N Engl J Med 2004;351(20):2035-37(editorial).
African-American patients may have a lower bioavailability of nitric oxide than Caucasian patients, increasing their level of cardiovascular risk. To test the benefit of a fixed dose of isosorbide dinitrate and hydralazine hydrochloride in African-Americans with severe heart failure, more than 1,000 African-American patients with left ventricular ejection fractions of < 35%, who were already receiving standard therapy at 161 United States centers, were randomized to receive active drug or placebo. The study was terminated early after 3 years due to a significantly higher death rate in the placebo group than in the therapy group (10.2% vs. 6.2%, p =0.02). A dose of 75 mg hydralazine and 40 mg of isosorbide three times daily led to a 43% reduction in 1-year mortality compared to standard therapy. Growing evidence supports the concept that nitric oxide protects against myocardial and vascular remodeling. Isosorbide has a vasodilatory effect by donating nitric oxide, and hydralazine prolongs the vasodilatory effects by preventing degradation of nitric oxide to superoxides. Because the population in this study was narrowly specified, it remains unknown whether these two drugs in combination with an angiotensin-converting enzyme (ACE) inhibitor would improve survival among patients with heart failure in general or among patients in other racial groups beyond that achieved by ACE inhibitor alone.