To compare the benefit of angiotensin-converting enzyme inhibition and direct vasodilation on the prognosis of advanced heart failure, 117 patients evaluated for cardiac transplantation who had severe symptoms and abnormal hemodynamic status at rest were randomized to treatment with either captopril or hydralazine plus isosorbide dinitrate (Hy-C Trial). Comparable hemodynamic effects of the two regimens were sought by titrating vasodilator doses to match the hemodynamic status achieved with nitroprusside and diuretic agents, attempting to achieve a pulmonary capillary wedge pressure of 15 mm Hg and a systemic vascular resistance of 1,200 dynes.s.cm-5. Treatment with the alternate vasodilator was started because of poor hemodynamic response or side effects (40% of patients in the captopril group and 22% in the hydralazine group). Adequate hemodynamic response in patients with a serum sodium level less than 135 mg/dl was more likely with hydralazine than with captopril (71% vs. 33%, p = 0.04). Isosorbide dinitrate was prescribed in 88% of the hydralazine-treated patients and 84% of the captopril-treated patients. The hemodynamic improvements from each regimen were equivalent. After 8 +/- 7 months of follow-up, the actuarial 1-year survival rate was 81% in the captopril-treated patients and 51% in the hydralazine-treated patients (p = 0.05). The improved survival with captopril resulted from a lower rate of sudden death, which occurred in only 3 of 44 captopril-treated patients compared with 17 of 60 hydralazine-treated patients (p = 0.01). In the subset of patients who continued treatment with the initial vasodilator, results were similar to those for the entire treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)