HEART-FAILURE AND NITRATES

Nitrates remain largely prescribed in heart failure. Their haemodynami c effects, a consequence of venous vasodilatation, have been clearly d emonstrated in the acute situation, where they induce a fall in pulmon ary pressure and left ventricular end-diastolic pressure, associated, at high doses, with an arterial vasodilator effect. Haemodynamic escap e phenomena are observed during chronic administration and the periphe ral vasodilator effect, in particular, tends to fade. Although, togeth er with depletion of sulfhydryl radicals, activation of vasoconstricto r neuroendocrine systems, associated with haemodilution, plays an impo rtant role in this escape, coprescription of angiotensin converting en zyme inhibitors or diuretics has been shown to be unable to prevent th ese effects. The effects of nitrates on the exercise capacity remain c ontroversial, although the combination of isosorbide dinitrate-hydrala zine induced a significantly greater increase of maximal oxygen consum ption than enalapril, together with a more marked increase in the ejec tion fraction. No trial has assessed the effects on mortality of nitra tes, used as the only vasodilator agent, in heart failure, but in stud ies V-HeFT 1 and 2, the combination of isosorbide dinitrate-hydralazin e significantly improved survival, with a 38 % reduction of mortality at one year compared to placebo or prazosin groups. However, this redu ction remained less than that obtained with enalappril. In the case of contraindication or impossibility of using angiotensin converting enz yme inhibitors, a combination of high doses of nitrates and hydralazin e may be justified. On the other hand, when angiotensin converting enz yme inhibitors are already prescribed, nitrates can only be considered to improve symptoms in the case of persistence of dyspnoea. However, due to the hypotension which they can induce, their use should not int erfere with the administration of the high doses of angiotensin conver ting enzyme inhibitor required. The dose of nitrates should then be de termined as a function of their efficacy on symptoms and the blood pre ssure tolerance, while allowing an interval of at least ten hours in o rder to attenuate the escape phenomenon.