Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction: A clinical perspective
Hydralazine and nitrates have long been parts of many studies for their potential benefits in heart failure with reduced ejection fraction (HFrEF). These agents have been used in combination and/or separately. Before the advent of ACEi these agents showed a significant improvement in symptoms, survival and repeated hospitalizations. Currently they are used alone or in combination with ACEi in addition to other heart failure medications.Various studies have shown the clinical benefits of decreasing vascular resistance in patients with HFREF. Left ventricular function largely depends on preload and afterload. So by modifying these two with the above agents proved to be very helpful in HFrEF Isosorbide dinitrate is a venodilator and hydralazine is an arterial dilator. Nitrates act as NO donors, while hydralazine acts as an antioxidant through the reduction of NO consumption. One pivotal study on sodium nitroprusside in heart failure in patients with acute MI showed reduction in left ventricular filling pressures from 22.7±2.0 to 11.3±1.6 mm Hg and led to a modest increase in cardiac output 1. In another study, sodium nitroprusside showed reduction in systemic vascular resistance and left ventricular filling pressure of 50% and 47% respectively and an increase in cardiac output of 56% 2. So these beneficial effects on hemodynamics led to the studies with oral agents like isosorbide dinitrate and hydralazine. Massie et al studied the combination of hydralazine and ISDN (H-ISDN) in class III to IV heart failure patients in 1977, suggesting that simultaneously reducing afterload with hydralazine and preload with ISDN would result in a better response than with either drug alone. They found that H-ISDN caused reduction of both left ventricular filling pressure and systemic vascular resistance by 36% & 34% respectively and an increase in cardiac index by 58% 3.