[Cardiac failure and nitrates]

Nitrates remain largely prescribed in heart failure. Their haemodynamic effects, a consequence of venous vasodilatation, have been clearly demonstrated in the acute situation, where they induce a fall in pulmonary pressure and left ventricular end-diastolic pressure, associated, at high doses, with an arterial vasodilator effect. Haemodynamic escape phenomena are observed during chronic administration and the peripheral vasodilator effect, in particular, tends to fade. Although, together with depletion of sulfhydryl radicals, activation of vasoconstrictor neuroendocrine systems, associated with haemodillution, plays an important role in this escape, coprescription of angiotensin converting enzyme inhibitors or diuretics has been shown to be unable to prevent these effects. The effects of nitrates on the exercise capacity remain controversial, although the combination of isosorbide dinitrate-hydralazine induced a significantly greater increase of maximal oxygen consumption than enalapril, together with a more marked increase in the ejection fraction. No trial has assessed the effects on mortality of nitrates, used as the only vasodilator agent, in heart failure, but in studies V-HeFT 1 and 2, the combination of isosorbide dinitrate-hydralazine significantly improved survival, with a 38% reduction of mortality at one year compared to placebo or prazosin groups. However, this reduction remained less than that obtained with enalapril. In the case of contraindication or impossibility of using angiotensin converting enzyme inhibitors, a combination of high doses of nitrates and hydralazine may be justified. On the other hand, when angiotensin converting enzyme 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 interfere with the administration of the high doses of angiotensin converting enzyme inhibitor required. The dose of nitrates should then be determined as a function of their efficacy on symptoms and the blood pressure tolerance, while allowing an intervel of at least ten hours in order to attenuate the escape phenomenon.