The place of ACE inhibitors in the current treatment of chronic heart failure

Abstract

In assessing the place of any therapy for chronic heart failure (CHF) there are two main considerations does the treatment make patients feel better and does it make them live longer? It is then important to see whether this treatment offers any advantages over other treatments; here the side effect profile may be a crucial determinant. There is now sufficient evidence to compare angiotensin converting enzyme (ACE) inhibitors to diuretics and other vasodilators in these respects (but not enough to make any comparison with digoxin). With regard to symptomatology, several well designed large scale, placebo-controlled trials have shown that ACE inhibitors improve symptoms and exercise tolerance in advanced CHF when added to diuretics (and other treatments). 1-3 In less severe CHF the evidence is different. Richardson et al. have shown that an ACE inhibitor alone may be an insufficient treatment in patients with mild heart failure compared to a diuretic alone, especially if there is a previous history of acute pulmonary oedema.4 It has also been suggested that increasing the dose of diuretic may improve symptoms and exercise tolerance more than adding an ACE inhibitor in patients with mild to moderate CHF.5 The combination of an ACE inhibitor, it should be stressed, does cause some clinical improvement and considerations other than symptomatic benefit may be important in deciding whether to add an ACE inhibitor or more diuretic (see below).6'7 In contrast to the case with diuretics, there is good evidence to suggest that ACE inhibitors are superior to other vasodilators in terms of symptomatic benefit and also in terms of side effects, tachyphylaxis and neuroendocrine suppression.8 10 Turning to mortality, there is no evidence to show that diuretics improve prognosis in CHF and some suspicion that they may contribute to progression of the syndrome (see below). Certain vasodilators, on the other hand, may reduce mortality. The VHeFT-1 trial compared a high dose hydralazine isosorbide dinitrate (ISDN) combination (300mg/160mg daily respectively), prazosin (20mg daily) and placebo as adjunctive therapy in patients with mild to moderate heart failure.1' Prazosin was not superior to placebo but the hydralazine ISDN combination reduced mortality from 19.5% to 12.1% after 1 year. The patients in this study were, however, atypical there was a high incidence of alcohol-related disease (40%), a somewhat low incidence of coronary artery disease (44%) and all patients were male and relatively young (mean 58 years). Even more importantly approximately one-third of patients had to have a reduction in dosage, or the discontinuation of either or both drugs, during this study because of adverse effects. More recently the Consensus trial study group have reported that the addition of enalapril (mean daily dose 18.4mg) to maximal conventional treatment in patients with severe CHF resulted in a reduction in 1 year mortality from 52% to 31%.12 The patients in this study were much more typical of British hospital practice 73% had coronary artery disease, they were of both sexes and had a mean age of 70 years. Also in contrast to the VHeFT-1 trial, there was a much lower incidence of serious adverse effects (17% withdrawn on enalapril compared with 14% on placebo). Crucially, 44% of the enalapril-treated patients were already receiving other vasodilators (mainly ISDN) and yet still showed a reduction in mortality. All this information suggests that ACE inhibitors do indeed make patients with CHF feel better and live longer. They seem to be more effective than other vasodilators in these respects and certainly have fewer adverse effects.9 ACE inhibitors must, however, remain complementary to diuretics. The latter offer initially superior symptom control but do not improve prognosis. There are also other reasons to believe that ACE inhibitors and diuretics