What is the role of hydralazine and isosorbide dinitrate in the treatment of heart failure?

Because vascular capacitance and resistance are important determinants of cardiac performance, peripheral vasodilators can produce striking hemodynamic benefits in patients with heart failure. By dilating capacitance vessels, venodilators can decrease right and left ventricular volumes and pressures. By dilating resistance vessels, arterial vasodilators can increase ventricular ejection and decrease valvular regurgitation. These hemodynamic benefits have led to the widespread use of intravenous direct-acting vasodilators for the short-term treatment of patients with acutely decompensated heart failure. However, the long-term use of many direct-acting vasodilators has not produced consistent benefits and has increased the risk of decompensated heart failure and death, possibly because these drugs may not correct cardiovascular remodeling and may have adverse effects on the heart or circulation.

The only favorable experience with long-term vasodilator therapy in heart failure has been with the combination of hydralazine and isosorbide dinitrate. Although the two drugs were initially combined because of their complementary dilation of peripheral blood vessels, recent evidence suggests that they act

Further reading

Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Am J Cardiol. 1999;83:1 A-38A. principally at a biochemical level rather than as conventional vasodilators. Hydralazine may have antioxidant effects that interfere with the biochemical and molecular mechanisms responsible for the progression of heart failure and the development of nitrate tolerance, while nitrates may inhibit abnormal myocardial and vascular growth and hence attenuate the process of ventricular remodeling.

Relatively high doses of hydralazine (up to 300 mg) in combination with high-dose isosorbide dinitrate (up to 160 mg), without angiotensin-converting enzyme (ACE) inhibition, may have some beneficial effect on mortality, but not on hospitalization for heart failure. At these doses, the combination increases exercise performance more than enalapril, but without achieving the same reduction in mortality as an ACE inhibitor. There is no evidence of benefit when hydralazine or dinitrate is used alone in addition to current therapy. The combination of hydralazine and isosorbide dinitrate should not be used to treat heart failure in patients who have not yet received an ACE inhibitor, nor should it be used to replace a well-tolerated ACE inhibitor. As for a poorly tolerated ACE inhibitor, this is best replaced, not by combination hydralazine-dini-trate therapy, but by an angiotensin receptor blocker.

Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Eur Heart J. 2001 ;22:1527-1560.


drug; hydralazine; isosorbide dinitrate; vasodilator therapy; combination therapy; acute heart failure

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