The American journal of cardiology
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Review Comparative Study
Effects of nitrates and hydralazine in heart failure: clinical evidence before the african american heart failure trial.
The initial rationale for use of organic nitrates and hydralazine (HYD) in combination was their complementary "nitroprussidelike" hemodynamic effect caused by the predominant venodilatory action of organic nitrates and the arterial-dilatory effect of HYD. This combination leads to a significant improvement in cardiac function, with a concomitant reduction in right and left ventricular filling pressures and augmentation of cardiac output. Based on this hemodynamic profile, the Vasodilator Heart Failure Trial (V-HeFT) was designed to examine the effect of this drug combination on the outcome of patients with congestive heart failure (CHF). ⋯ Prevention of nitrate tolerance with HYD may also be responsible for the favorable therapeutic effects of combination ISDN-HYD. Frequent administration of ISDN has been shown to result in the early development of nitrate tolerance. Concomitant use of HYD with a nitrate, both in an animal model and in patients with CHF, has been shown to prevent the development of nitrate tolerance and maintain the favorable hemodynamic effect of nitrates.
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Review Comparative Study
The African American Heart Failure Trial: a clinical trial update.
Progressive vascular and myocardial remodeling in heart failure is effectively slowed by therapy with neurohormonal antagonists, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, aldosterone antagonists, and adrenergic-receptor blockers. These therapies, along with the correction of hemodynamic abnormalities, have dramatically reduced morbidity and mortality in patients with heart failure. Endothelial dysfunction, increased oxidative stress, and decreased bioavailability of nitric oxide (NO) also occur in heart failure. ⋯ The A-HeFT confirms the benefit of fixed-dose ISDN-HYD, which may enhance NO bioavailability in African American patients with NYHA class III-IV heart failure and suggests that NO-enhancing therapy is an effective new treatment strategy for heart failure. In addition, the A-HeFT affirms the critical importance of the inclusion of population subgroups in clinical trials both as a way to probe for pathophysiologic mechanisms of disease and to devise optimal treatment strategies. The rich and unique A-HeFT database will provide new opportunities to understand the pathophysiology and management of heart failure.