HEART FAILURE
Clinical Overview

Pharmacotherapy

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Isosorbide Dinitrate and Hydralazine

Indications Should be used routinely for severe heart failure due to left-ventricular systolic dysfunction1 Add for mild to moderate heart failure patients who remain symptomatic after optimal ACE inhibitor and diuretic therapy Improves symptoms and exercise tolerance; prevents clinical deterioration1

The combination of HYD/ISDN is an appropriate alternative in patients with contraindications or intolerance to ACE inhibitors.¹ This combination is not as beneficial as the ACE inhibitors in reducing mortality, although they have been shown to increase exercise capacity as much as enalapril.⁹ Side effects are a significant problem and include headache, nausea, dizziness, and tachycardia. Weekly titrations of both hydralazine and isosorbide dinitrate are necessary; with initial doses of 25 mg three times daily and 10 mg three times daily respectively. Those with low blood pressure, severe heart failure, or advanced age can be started at 10 mg three times daily for both agents.¹ The dosing of isosorbide dinitrate should allow for at least a 10 hour drug-free period to minimize the chanced of nitrate tolerance.²⁸ This combination is not FDA-approved for management of heart failure.

The Veterans Administration Heart Failure Trials (V-HeFT I and V-HeFT II)⁹ ,²⁹ demonstrated both short-term and long-term benefits from the combination of hydralazine / isosorbide dinitrate (HYD/ISDN) as compared to placebo. The V-HeFT I trial also included prazosin, another vasodilator. In this trial, prazosin was found to have mortality effects similar to placebo.

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