BiDil (isosorbide dinitrate and hydralazine): a new fixed-dose combination of two older medications for the treatment of heart failure in black patients.

BiDil is a new fixed-dose combination of 2 older medications, isosorbide dinitrate (ISDN) and hydralazine. ISDN is an organic nitrate that is biotransformed into nitric oxide, a potent vasodilator. Hydralazine is believed to have both vasodilatory properties specific to the arteries and antioxidant properties, which address both the biochemical alterations in the failing cardiovascular system as well as the issue of nitrate tolerance. A drug regimen combining an NO stimulator (ISDN) with an antioxidant (hydralazine) favorably influences the nitroso-redox balance. Retrospective analyses of previous heart failure (HF) clinical trials comparing the combination of ISDN and hydralazine with placebo and enalapril, respectively, demonstrated a benefit in the black population, setting the precedent for a race-based therapeutic study, the African-American Heart Failure Trial (A-HeFT). A-HeFT examined the use of BiDil added to standard HF therapy in blacks with New York Heart Association functional class III and IV HF. BiDil demonstrated a 43% reduction in mortality when compared with placebo. As a result, current evidence-based treatment guidelines recommend that the addition of ISDN and hydralazine in black patients with moderate to severe HF optimized on standard therapy be considered. BiDil is currently indicated for the treatment of HF as an adjunct to standard therapy in black patients. The use of BiDil for black patients with mild disease or in nonblack patients with HF has not been studied. Future clinical trials involving an ethnically and clinically diverse population of patients would further define the role of combined ISDN and hydralazine in the treatment of HF.

BiDil: assessing a race-based pharmaceutical.

Isosorbide and hydralazine in a fixed-dose combination (BiDil) has provoked controversy as the first drug approved by the Food and Drug Administration marketed for a single racial-ethnic group, African Americans, in the treatment of congestive heart failure. Family physicians will be better prepared to counsel their patients about this new drug if they understand a number of background issues. The scientific research leading to BiDil's approval tested the drug only in African American populations, apparently for commercial reasons, so the drug's efficacy in other populations is unknown. Race as a biological-medical construct is increasingly controversial; BiDil offers a good example of how sociocultural factors in disease causation may be overlooked as a result of an overly simplistic assumption of a racial and hence presumed genetic difference. Past discrimination and present disparities in health care involving African American patients are serious concerns, and we must welcome a treatment that promises to benefit a previously underserved group; yet the negative aspects of BiDil and the process that led to its discovery and marketing set an unfortunate precedent. Primary care physicians should be aware of possible generic equivalents that will affect the availability of this drug for low-income or uninsured patients.

Cost-effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine therapy for blacks with heart failure.

BACKGROUND: Fixed-dose combination of isosorbide dinitrate/hydralazine (ISDN/HYD) improved clinical outcomes in the African-American Heart Failure Trial (A-HeFT). We assessed the resource use, costs of care, and cost-effectiveness of ISDN/HYD therapy in the A-HeFT trial population. METHODS AND RESULTS: We obtained resource use data from A-HeFT, assigning costs through the use of US federal sources. Excluding indirect costs, we summarized the within-trial experience and modeled cost-effectiveness over extended time horizons, including a US societal lifetime reference case. During the mean trial follow-up of 12.8 months, the ISDN/HYD group incurred fewer heart failure-related hospitalizations (0.33 versus 0.47 per subject; P=0.002) and shorter mean hospital stays (6.7 versus 7.9 days; P=0.006). When study drug costs were excluded, both heart failure-related and total healthcare costs were lower in the ISDN/HYD group (mean per-subject heart failure-related costs, 5997 dollars versus 9144 dollars; P=0.04; mean per-subject total healthcare costs, 15,384 dollars versus 19,728 dollars; P=0.03). With an average daily drug cost of 6.38 dollars, ISDN/HYD therapy was dominant (reduced costs and improved outcomes) over the trial duration. Assuming that no additional benefits accrue beyond the trial, we project the cost-effectiveness of ISDN/HYD therapy using heart failure-related costs to be 16,600 dollars/life-year at 2 years after enrollment, 37,100 dollars/life-year at 5 years, and 41,800 dollars/life-year over lifetime (reference case). CONCLUSIONS: ISDN/HYD therapy, previously shown to improve clinical outcomes, also reduced resource use and costs in A-HeFT, primarily because of a large reduction in hospitalizations. Long-term use of ISDN/HYD therapy should be associated with a favorable cost-effectiveness profile in this population.