1. Home>
2. Specialties>
3. Cardiology>
4. Summary and Comment

An Old Drug Combination Tested in Black Patients

Does isosorbide-hydralazine combination therapy have a role in treating black patients with heart failure?

The combination of isosorbide dinitrate and hydralazine lost favor in the treatment of heart failure (HF) after the ACE inhibitor enalapril proved to be superior in the V-HeFT II trial more than a decade ago. However, subsequent research has suggested that ACE inhibitors might not be as effective in black patients as in white patients (Journal Watch Cardiology Jun 15 2001). One theory is that genetic variability may underlie drug-response variation among racial groups. There is some evidence of racial differences in the bioavailability of nitric oxide and in renin-angiotensin activity, both of which isosorbide-hydralazine combination therapy might address.

These researchers conducted a multicenter, randomized trial of placebo versus a fixed-dose isosorbide-hydralazine combination regimen (target dose, 40 mg isosorbide dinitrate plus 75 mg hydralazine, thrice daily) in 1050 patients with NYHA class III-IV HF (mean age, 57; 41% with diabetes) who identified themselves as black. All had LV ejection fractions <35% (or <45% with LV dilation) and continued to receive standard HF therapy; their mean weight was 93 kg, and the most common primary cause of HF was hypertension. The study was funded by the manufacturer of an isosorbide-hydralazine combination regimen that the FDA has not yet approved.

The trial was terminated early (mean follow-up, 10 months) when a significant benefit of active treatment became evident for all components of the primary endpoint: all-cause mortality (6% with isosorbide-hydralazine vs. 10% with placebo), first hospitalization for HF (16% vs. 24%), and questionnaire-assessed quality of life. The most common adverse effects of active treatment were dizziness and headache.

Comment: Although this study was heralded in the press as having identified a drug for black patients, it did not test whether the response to the isosorbide-hydralazine regimen actually differed by race. What the study did show was that in HF patients who identified themselves as black, the combination regimen improved outcomes very effectively. Experts continue to debate how this information should best be translated into practice, and whether differential treatment by self-defined race is sound medicine.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology December 17, 2004

Citation(s):

Taylor AL et al. for the African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004 Nov 11; 351:2049-57.

• Original article (Subscription may be required)
• 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)