For years, the standard drug therapy for heart failure has included diuretics, [beta]-blockers, angiotensin-converting enzyme (ACE) inhibitors, and digoxin. The higher prevalence of the condition in blacks than in whites has been known, as has the fact that compensating for the impaired bioavailability of nitric oxide, using a combination of isosorbide dinitrate and hydralazine, an antioxidant, can improve outcomes. Now, in a novel approach to the study of heart failure, scientists examined the use of these two drugs, along with standard therapy, specifically in blacks-a group that has responded well to the combination in larger studies of the general population. The study examined the drugs' effect on a combination of factors: death from any cause, a first hospitalization for heart failure, and a deterioration in quality-of-life scores.
The trial was ended earlier than planned because of a dramatic difference in the interim mortality rates: 10.2% in the placebo group (54 deaths in the 532 subjects receiving standard therapy) versus 6.2% in the treatment group (32 of the 518 receiving standard therapy plus the fixed-dose combination). In addition, survival over time in the two groups began to diverge at 180 days, and the differences were not only sustained thereafter but widened. In fact, the treatment outperformed the placebo in every outcome category studied.
Caveat lector.
Although these findings are undeniably impressive, an accompanying editorial imputes a note of caution: the study authors have financial ties to NitroMed, the company that funded the study and has licensed the patents for the use of the combinations of hydralazine and both isosorbide dinitrate and mononitrate from study coauthor Jay N. Cohn. NitroMed subsequently applied for and was granted a patent on the use of the combination in black patients. And the study authors admit that they chose this population to study because earlier studies indicated they were likely to have success.
According to the editorial, "[T]he emergence of the combination treatment as a race-specific drug was driven in large measure by regulatory and market incentives. It remains unknown whether these two drugs in combination with an ACE inhibitor improve survival among patients with heart failure in general . . . beyond the improvement achieved by ACE inhibition alone. But a treatment for all patients with heart failure, regardless of race, could not have extended NitroMed's intellectual property protection by 13 years."-Doug Brandt
Taylor AL, et al. N Engl J Med 2004;351(20):2049-57; Bloche MG. N Engl J Med 2004;351(20):2035-7.