Effect of direct vasodilation with hydralazine versus angiotensin-converting enzyme inhibition with captopril on mortality in advanced heart failure: The Hy-C trial

Abstract

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)

Angiotensin Subtype 1 Receptor (AT1) Blockade Improves Vasorelaxation in Heart Failure by Up-Regulation of Endothelial Nitric-Oxide Synthase via Activation of the AT2Receptor

“…While treating patients with heart failure, afterload reduction with AT 1 blockade is generally thought to be comparable to that of an angiotensin-converting enzyme inhibitor, it is not clear whether this is due to the blunting of the vasoconstrictive effect of ANG II alone or additionally through a secondary mechanism that enhances nitric oxide (NO)-mediated endothelial vasorelaxation. This may be crucial since it appears that afterload reduction alone with arterial vasodilators without specific effects on endothelial function have had essentially no beneficial effects on left ventricular (LV) remodeling and mortality in patients with congestive heart failure (Fonarow et al, 1992). In contrast, therapy that improves endothelial function also attenuates LV remodeling and enhances survival in heart failure (The SOLVD Investigators, 1988;Kubo et al, 1991;Katz et al, 1992;Drexler et al, 1993).…”

Rapid clinical assessment of hemodynamic profiles and targeted treatment of patient with acutely decompensated heart failure

“…5 Intravenous vasodilator therapy has not been associated with a worsening of myocardial ischemia (and actually reduces myocardial oxygen consumption) or the precipitation of ventricular arrhythmias, 3 and can ease and speed the transition to an oral regimen of an ACE inhibitor and diuretic. 22 A significant reduction (and near normalization) in ventricular filling pressures can be achieved with IV vasodilators and diuretics within 3 to 24 h in decompensated patients with HF with the wet and warm profile and the wet and cold profile with elevated SVR. These improved hemodynamics can be maintained over the following 8 months with an oral regimen of an ACE inhibitor and a diuretic.…”

Rethinking the Focus of Heart Failure Quality Measures

“…Furthermore, drug classes may have a differential impact on mortality even when titrated to similar hemodynamic indices. 13 The increasing complexity of medical regimens for HF poses substantial logistical and financial challenges to patients and threatens to erode compliance. Although not well studied in HF, data from other diseases show a clear signal for reduced…”