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The rationale for the combined use of hydralazine and nitrates was to achieve both venous and arterial vasodilation. A post hoc retrospective analysis of 2 vasodilator trials demonstrated particular efficacy of isosorbide dinitrate and hydralazine in the black cohort91.

A confirmatory trial has been done. In that trial, which was limited to the black population with HF, the addition of hydralazine and isosorbide dinitrate to therapy with an ACEI and/or a beta-blocker was shown to be of significant benefit92. The benefit was presumed to be related to enhanced nitric oxide bioavailability. Whether this benefit is evident in other patients with HF remains to be investigated.

The combination of hydralazine and isosorbide dinitrate should not be used for the treatment of HF in patients who have no prior use of an ACEI and should not be substituted for ACEIs in patients who are tolerating ACEIs without difficulty.

Despite the lack of data with the vasodilator combination in patients who are intolerant of ACEIs, the combined use of hydralazine and isosorbide dinitrate may be considered as a therapeutic option in such patients.

However, compliance with this combination has generally been poor because of the large number of tablets required and the high incidence of adverse reactions93. For patients with more severe symptoms and ACEI intolerance, the combination of hydralazine and nitrates is used frequently, particularly when ACEI therapy is limited by hypotension or renal insufficiency.

There are, however, no trials addressing the use of isosorbide dinitrate and hydralazine specifically in the population of patients who have persistent symptoms and intolerance to inhibitors of the renin-angiotensin system.

A summary of the cardiovascular drugs most useful for the treatment of the various stages of HF is provided in the table below:

91 Loeb HS, Johnson G, Henrick A, Smith R, Wilson J, Cremo R, Cohn JN. Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group. Circulation 1993;87 Suppl:V178–V87.

92 Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351:2049 –57.

93 Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study. N Engl J Med 1986;314:1547–52.

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