Current Controversies with ACE Inhibitor Treatment in Heart Failure

Although the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on symptoms, morbidity and mortality have been proven beyond any doubt, some controversies remain. First, surveys have shown that a minority of patients in whom ACE inhibition is indicated, actually receive ACE inhibitors. Moreover, the majority of patients on ACE inhibitors use doses that are far lower than the target dose used in the large trials. These lower doses may be less effective. There is limited evidence to show that low-dose ACE inhibition is as effective as high-dose ACE inhibition. However, two ongoing trials – ATLAS and NETWORK – will determine the relative efficacy of high- and low-dose ACE inhibition. Second, the large ACE inhibitor trials have shown major variations in mortality, suggesting that differences between the efficacy of ACE inhibitors exist. However, the major differences in mortality are related mainly to the variations in inclusion criteria, suggesting a class effect of ACE inhibition. A study, assessing the relative efficacy of various ACE inhibitors seems unrealistic at this time. Third, mortality data on asymptomatic left ventricular dysfunction are conflicting, suggesting that initial treatment can wait until symptoms of heart failure appear. However, studies are consistent in showing reduction of events. Thus, early treatment in asymptomatic dysfunction may be warranted. Finally, it has been demonstrated that ACE inhibitors act favorably on volume and pressure overload, electrolytes and autonomic function. Nevertheless, the ACE inhibitor trials have failed to demonstrate that reduction of mortality is related to reduction of malignant ventricular arrhythmias/sudden death. This issue needs further study as specific antiarrhythmic strategies may be appropriate for arrhythmias.