Impact of ISDN-hydralazine on mortality and morbidity of African-American patients with Heart Failure A-Heft Trial Presented at American Heart Association Scientific Sessions 2004 Presented by Dr. A.L. Taylor

www. Clinical trial results.org Isosorbide dinitrate (ISDN) plus hydralazine Tablet containing 20 mg ISDN and 37.5 mg hydralazine (BiDil ®, NitroMed) 3X daily. Dosage could be doubled by enrolling physician. n= % female 44.8% diabetic Isosorbide dinitrate (ISDN) plus hydralazine Tablet containing 20 mg ISDN and 37.5 mg hydralazine (BiDil ®, NitroMed) 3X daily. Dosage could be doubled by enrolling physician. n= % female 44.8% diabetic Primary Endpoint:  Weighted composite of all-cause death, first hospitalization for heart failure, and change in quality of life at a mean follow-up of 10 months Primary Endpoint:  Weighted composite of all-cause death, first hospitalization for heart failure, and change in quality of life at a mean follow-up of 10 months A-Heft Trial Presented at AHA 2004 Placebo  n= % female 37.0% diabetic Placebo  n= % female 37.0% diabetic 1,050 African-American patients with advanced heart failure New York Heart Association (NYHA) class 3-4 for > 3 months LV function < 35% (< 40% if LV dilated per echo) 90% receiving diuretics, 69% ACE-inhibitor, 17% angiotensin receptor blocker, 74% beta-blocker 1,050 African-American patients with advanced heart failure New York Heart Association (NYHA) class 3-4 for > 3 months LV function < 35% (< 40% if LV dilated per echo) 90% receiving diuretics, 69% ACE-inhibitor, 17% angiotensin receptor blocker, 74% beta-blocker

www. Clinical trial results.org A-Heft Trial: Primary Endpoint Presented at AHA 2004 Primary Composite Score p = 0.01 The primary weighted composite of all-cause mortality, first hospitalization for HF and change in quality-of-life was significantly lower in the ISDN- hydralazine group than in the placebo group at a mean follow- up of 10 months

www. Clinical trial results.org A-Heft Trial: Primary Endpoint Presented at AHA 2004 All individual components of the primary composite endpoint were significantly improved with ISDN-hydralazine therapy, namely death, first hospitalization for heart failure, and change in the quality-of-life score (a larger negative score indicates a better quality of life).

www. Clinical trial results.org A-Heft Trial: Mortality Presented at AHA 2004 Mortality p = 0.01 A significant reduction in mortality in the ISDN- hydralazine group began to emerge at 6 months and continued to diverge through follow-up, prompting an early end to the trial

www. Clinical trial results.org A-Heft Trial: Adverse effects Presented at AHA 2004 Adverse events of headache and dizziness were significantly higher in the ISDN- hydralazine group, while the more serious adverse events of exacerbation of CHF were significantly lower in the ISDN-hydralazine group than in the placebo group p=<0.001 p=0.04 p=0.005

www. Clinical trial results.org A-Heft Trial: Summary Among African-American patients with advanced heart failure, the primary weighted composite of all-cause death, first hospitalization for heart failure, and change in quality of life was significantly lower in the ISDN-hydralazine group than in the placebo group at a mean follow-up of 10 months All individual components of the primary endpoint were significantly improved with ISDN-hydralazine therapy compared to placebo The trial was stopped after 1,050 of the planned 1,100 patients had been enrolled due to the significantly lower incidence of mortality in the ISDN- hydralazine group This was the first study of this therapy to be conducted solely in African- American patients, a population disproportionately affected by heart failure Future studies are warranted for the identification of genetic markers more specific to drug efficacy to replace the broader category of race as a treatment criteria Among African-American patients with advanced heart failure, the primary weighted composite of all-cause death, first hospitalization for heart failure, and change in quality of life was significantly lower in the ISDN-hydralazine group than in the placebo group at a mean follow-up of 10 months All individual components of the primary endpoint were significantly improved with ISDN-hydralazine therapy compared to placebo The trial was stopped after 1,050 of the planned 1,100 patients had been enrolled due to the significantly lower incidence of mortality in the ISDN- hydralazine group This was the first study of this therapy to be conducted solely in African- American patients, a population disproportionately affected by heart failure Future studies are warranted for the identification of genetic markers more specific to drug efficacy to replace the broader category of race as a treatment criteria