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Hydralazine plus nitrate therapy in patients with heart failure with reduced ejection fraction

Wilson S Colucci, MD
Section Editor
Stephen S Gottlieb, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


Hydralazine plus nitrate therapy provides symptomatic and mortality benefit in selected patients with heart failure with reduced ejection fraction (HFrEF; also known as HF due to systolic dysfunction or systolic HF) [1].

Recommendations for use of hydralazine plus nitrates in patients with HFrEF and data supporting the efficacy of this drug combination will be presented here. An overview of the treatment of HFrEF is presented separately (figure 1). (See "Overview of the therapy of heart failure with reduced ejection fraction".)


A hemodynamic rationale for the combined use of hydralazine and nitrate therapy is to reduce cardiac preload and afterload by achieving both venous and arterial vasodilation. Hydralazine is an arterial vasodilator and nitrates are predominantly venodilators. These vasodilatory effects can reduce intracardiac filling pressures, which may reduce adverse cardiac remodeling. (See "Cardiac remodeling: Basic aspects".)

It has also been hypothesized that combined hydralazine and nitrate therapy enhances nitric oxide bioavailability since nitrates serve as nitric oxide donors and hydralazine is an antioxidant that reduces consumption of nitric oxide [1-3]. It has been postulated that this protective mechanism can be recruited even in the presence of neurohormonal blockade (eg, use of angiotensin converting enzyme inhibitors).


Our approach

Indications — For select patients with heart failure with reduced ejection fraction (HFrEF), we recommend hydralazine plus oral nitrate as a component of therapy. Our recommendations are similar to major society guidelines (figure 1) and are based on the clinical trial evidence discussed below. The strength of the evidence for benefit is somewhat stronger in black patients than in other patient groups, as reflected in our recommendations. (See 'Major society guidelines and regulations' below and 'Evidence of benefit' below.)

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Literature review current through: Nov 2017. | This topic last updated: Jul 12, 2016.
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